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Mahmoud Elahdadi Salmani

Associate Professor of Physiology

Education

  • Ph.D. 2003-2008

    Physiology

    TarbiatModares University, Tehran, Iran

  • M.Sc. 2003

    Physiology

    TarbiatModares University, Tehran, Iran

Selected Publications

Bahramzadeh Zoeram, S., Elahdadi Salmani, M., Lashkarbolouki, T., Goudarzi, I. Hippocampal orexin receptor blocking prevented the stress induced social learning and memory deficits (2019) Neurobiology of Learning and Memory, 157, pp. 12-23.

DOI: 10.1016/j.nlm.2018.11.009

Stress as a homeostatic challenge leads to the malfunction of learning and memory processes, namely social learning and memory. The orexin system is involved in stress responses through connections to the hypothalamic-pituitary axis (HPA). In addition, the hippocampus, a structure vulnerable to stress-induced changes, expresses orexin receptors 1 and 2 (OXr1 and OXr2) in various sub-regions. The present study is aimed at assessing the effects of hippocampal orexin receptor blockade on social learning and memory impairments and anxiety development following stress. Male Wistar rats (220–250 g) underwent cannula implantation in the hippocampus. Acute (two mild electric shocks, 5.5 mA) and chronic stresses (ten days of restraint, 6 h daily) were applied with or without injection of orexin receptor antagonists (SB-334867 or TCS OX 29). Sociability and social novelty in animals were assessed in a three-chamber social maze at the end of stress application. Anxiety and exploratory behavior of animals were then examined, with 20 min intervals, using the open field (OF) and elevated plus maze (EPM) tests, respectively. Cisterna Magna cerebro-spinal fluid (CSF) was drained, before sacrifice, for orexin (OX) assay and trunk blood was collected to measure the plasma corticosterone (CRT). Neither the acute nor the chronic stress could affect the sociability. The acute but not chronic stress prevented the animal from sniffing the familiar caged rat in the novelty session, a response which was reversed following the blockade of both OXRs. Furthermore, acute but not chronic stress, led to increased anxiety and immobility behavior which were both impeded by blocking the orexin receptor (OXR). Conversely, OX content in CSF increased due to chronic restraint stress, an effect that was reversed by orexin blockade. Finally, elevated plasma CRT was recorded in response to both acute and chronic stresses. The observed increase in plasma CRT in chronically-stressed rats was abolished following inhibition of OXRs, however a similar effect was not seen in the acute-stress group. Our results identify hippocampal OXRs as potential candidates capable of preventing acute stress-induced impairments of social novelty and anxiety behavior, and chronic stress-induced plasma CRT and CSF orexin, changes. OXR manipulation may improve adaptation to stress pathophysiology. © 2018 Elsevier Inc.

AUTHOR KEYWORDS: Anxiety; Hippocampus; Orexin receptors; Social novelty; Stress

Koohpeyma, H., Goudarzi, I., Elahdadi Salmani, M., Lashkarbolouki, T., Shabani, M. Postnatal Administration of Homocysteine Induces Cerebellar Damage in Rats: Protective Effect of Folic Acid (2018) Neurotoxicity Research, . Article in Press.

DOI: 10.1007/s12640-018-9979-y

A widely held view suggests that homocysteine (Hcy) can contribute to neurodegeneration through promotion of oxidative stress. There is evidence that homocysteine is toxic to cerebellar Purkinje neurons in vitro; however, in vivo action of Hcy on Purkinje cell has not been investigated so far. Thus, this study was designed to evaluate the Hcy effects on neonatal rat cerebellum and cerebellar oxidative stress. We also evaluated the folic acid effects on biochemical alterations elicited by hyperhomocysteinemia (hHcy) in the cerebellum. Group I received normal saline, group II received Hcy subcutaneously twice a day at 8-h intervals (0.3–0.6 μmol/g body weight), group III received Hcy + folic acid (0.011 μmol/g body weight), and group IV received folic acid on postnatal day (PD) 4 until 25. On day 25, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in the cerebellum and motor cortex were assayed. Malondialdehyde (MDA) levels were also evaluated as a marker of lipid peroxidation. Rotarod and locomotor activity tests were performed in PD 25–27. Our results indicated that administration of Hcy increased plasma, cortical, and cerebellar total Hcy levels; reduced GPx activity; and induced lipid peroxidation in the cerebellum. Hcy impaired performance on the rotarod in rats. However, treatment with folic acid significantly attenuated motor coordination impairment, GPx activity reduction, the lipid peroxidation process, and significantly reduced plasma total Hcy levels. Histological analysis indicated that Hcy could decrease Purkinje cell count and folic acid prevented this toxic effect. We conclude that Hcy can induce neurotoxicity and folic acid has neuroprotective effects against cerebellar Hcy toxicity. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

AUTHOR KEYWORDS: Folic acid; Homocysteine; Oxidative stress; Purkinje cell; Rat

Moulaei, N., Mondanizadeh, M., Salmani, M.E., Palizvan, M.R., Khansarinejad, B., Sadegh, M. Transgenerational consequences of prepregnancy chronic morphine use on spatial learning and hippocampal Mecp2 and Hdac2 expression (2018) NeuroReport, 29 (9), pp. 739-744.

DOI: 10.1097/WNR.0000000000001025

There has recently been increasing interest in the transgenerational effects of opioids. Herein, transgenerational consequences of maternal chronic morphine consumption before gestation were investigated at the behavioral and molecular levels of next two generations. Twelve female Wistar rats were randomly divided into two groups: pregestation morphine-consuming and control mothers. Morphine-consuming mothers had access to morphine solution ad libitum for 2 months, whereas the control mothers received only tap water. One month after stopping morphine consumption, rats were mated. After parturition, male and female offspring and later grandoffspring of morphine-consuming and control mothers were divided and used as the study groups. Behavioral testing comprised spatial memory assessment using Morris water maze. Hippocampal expressions of Mecp2 and Hdac2 were investigated through real-Time PCR. Spatial memory was significantly diminished in male but not female offspring and grandoffspring of morphine-consuming mothers versus control (P<0.01). Hippocampal Mecp2 and Hdac2 were significantly upregulated in male but not in female offspring and grandoffspring of morphine-consuming mothers compared with control (P<0.05). Consequences of prepregnancy morphine consumption have sex differences and are detectable at the behavioral and molecular level over at least the next two generations. © 2018 Wolters Kluwer Health, Inc. All rights reserved.


AUTHOR KEYWORDS: epigenetic; memory; opioid; rat; transgenerational
INDEX KEYWORDS: histone deacetylase 2; methyl CpG binding protein 2; morphine; tap water, animal experiment; Article; birth; conception; controlled study; drug use; female; hippocampus; male; maternal exposure; Morris water maze test; mother; nonhuman; prepregnancy care; priority journal; progeny; protein expression; rat; real time polymerase chain reaction; sex difference; spatial learning; spatial memory; Wistar rat

Arzhang, A., Elahdadi Salmani, M., Lashkarbolouki, T., Goudarzi, I. Posterior hypothalamus glutamate infusion decreases pentylenetetrazol-induced seizures of male rats through hippocampal histamine increase (2017) Pharmacology Biochemistry and Behavior, 158, pp. 7-13.

DOI: 10.1016/j.pbb.2017.05.004

Objectives Seizures are epileptic manifestations that are intrinsically modulated through different neurotransmitters and receptor systems. Although glutamate increases excitation and hence seizures, it activates other systems which could potentially terminate seizures. Histamine originates from neurons of the posterior hypothalamus (PH) and can mediate anticonvulsant properties, but the effect of local PH glutamate on hippocampal histamine content is unknown. Therefore, in this study, the effect of PH glutamate and the involvement of hippocampal histamine in pentylenetetrazol (PTZ) induced seizure activity was studied. Materials and methods OX2R antagonist (TCS OX2 29, 40 nmol/1 μl, intra-PH), AMPA/Kainate receptor antagonist (CNQX, 3 mM, intra-PH) and glutamate (1 mM) were injected bilaterally into PH using stereotaxic surgery. The intravenous PTZ infusion model was used to generate behavioral convulsions and the amount of hippocampal histamine content was then measured using a biochemical method. Results Administration of glutamate into PH decreased both seizure stage and the duration of tonic-clonic convulsion (TCC) with increasing TCC latency and hippocampal histamine content. Blocking OX2Rs alone or coinhibition of OX2Rs and AMPA/kainate receptors reversed these effects by increasing both seizure stage and TCC duration, and by decreasing both latency and consequent histamine content. Conclusions Our findings suggest that glutamate administration into PH may control seizures (stages and duration) through increasing the hippocampal histamine content. © 2017 Elsevier Inc.

AUTHOR KEYWORDS: Glutamate receptor; Histamine; Orexin 2 receptor; Posterior hypothalamus; PTZ; Seizure
INDEX KEYWORDS: 6 cyano 7 nitro 2,3 quinoxalinedione; glutamic acid; histamine; pentetrazole; glutamic acid; pentetrazole, adult; animal experiment; animal model; animal tissue; Article; controlled study; drug effect; latent period; male; nonhuman; pentylenetetrazole-induced seizure; posterior hypothalamus; priority journal; rat; rat model; tonic clonic seizure; animal; chemically induced; drug effects; histamine release; hypothalamus; metabolism; pathophysiology; seizure; Wistar rat, Animals; Glutamic Acid; Histamine Release; Hypothalamus; Male; Pentylenetetrazole; Rats; Rats, Wistar; Seizures

Joushi, S., Elahdadi Salmani, M. Effect of eugenol on lithium-pilocarpine model of epilepsy: Behavioral, histological, and molecular changes (2017) Iranian Journal of Basic Medical Sciences, 20 (7), pp. 746-753.

DOI: 10.22038/ijbms.2017.9004

Objective(s): Epilepsy establishment gives rise to biochemical and morphological changes in the hippocampus. Oxidative stress, morphological changes, and mossy fiber sprouting (MFS) in the hippocampus underpin the epilepsy establishment. Eugenol is the main component of the essential oil extracted from cloves with the potential to modulate neuronal excitability. Therefore, we investigated the effect of eugenol on convulsive behavior, oxidative stress, and histological changes of the hippocampus in lithium- pilocarpine model of epilepsy. Materials and Methods: Male Wistar rats weighing 220–250 g were divided into 4 groups; Control, Pilocarpine, Eugenol-Pilocarpine, and Eugenol. Oxidative stress markers were assayed by a biochemical method. Nissl and Timm staining were used to show neuronal survival and MFS, respectively. Behavioral convulsions were evaluated using the modified Racine scale. Results: Eugenol decreased seizure stage and duration as well as mortality. Neuronal numbers were preserved by eugenol treatment in epileptic animals, while eugenol alone reduced the number by itself in all hippocampal sub-regions including DG, CA3, and CA1. Furthermore, eugenol alone increased MDA, GPx and SOD markers, while it increased MDA not only in combined treatment with pilocarpine but also in pilocarpine-treated animals. In contrast to MFS enhancement in naïve animals, eugenol partially reversed the MFS enhancement induced by pilocarpine. Conclusion: Eugenol could prevent behavioral convulsions and show neuroprotective effects through increasing neuronal survival probably by decreasing MFS and increasing the GPx antioxidant marker. © 2017, Mashhad University of Medical Sciences. All rights reserved.

AUTHOR KEYWORDS: Epilepsy; Eugenol; Hippocampus; Mossy fiber sprouting; Oxidative stress
INDEX KEYWORDS: eugenol; glutathione peroxidase; lithium; malonaldehyde; pilocarpine; superoxide dismutase; thiobarbituric acid reactive substance, animal model; animal tissue; Article; behavior assessment; biochemical analysis; brain histology; cell count; cell survival; controlled study; convulsion; experimental epilepsy; hippocampus; male; nonhuman; oxidative stress; protein content; rat

Sarfi, M., Elahdadi Salmani, M., Goudarzi, I., Lashkar Boluki, T., Abrari, K. Evaluating the role of astrocytes on β-estradiol effect on seizures of Pilocarpine epileptic model (2017) European Journal of Pharmacology, 797, pp. 32-38.

DOI: 10.1016/j.ejphar.2017.01.005

Epilepsy with periodic and unpredictable seizures is associated with hippocampal glutamate toxicity and tissue reorganization. Astrocytes play an important role in mediating the neuroprotective effects of estradiol and reducing seizure severity. Accordingly, the protective effects of low and high doses of estradiol on behavioral, astrocytic involvement and neuronal survival aspects of Pilocarpine-induced epilepsy were investigated. Lithium- Pilocarpine (30 mg/kg) model was used to provoke epilepsy. Βeta-estradiol (2,40 μg/µl) was injected subcutaneously from 48 before to 48 h after seizure induction. Behavioral convulsions were then monitored and recorded on the day of induction. Four weeks later, glutamine synthetase (GS) activity and the astrocyte transporter GLT-1 expression of the hippocampus were measured. Moreover, hippocampal glutamate and GABA were evaluated to study excitability changes. Finally, neuronal counting in the hippocampus was also performed using Nissl staining. The latency for generalized clonic (GC) convulsions significantly increased while the rate of GC and death significantly reduced due to β-estradiol treatment. GS activity and GLT-1 expression increased in the groups receiving the high dose of β-estradiol and Pilocarpine. Furthermore, the amount of both GABA and glutamate content decreased due to high dose of estradiol, while only GABA increased in Pilocarpine treated rats. Finally, administration of β-estradiol with low and high doses increased and improved the density of nerve cells. It is concluded that chronic administration β-estradiol has anticonvulsant and neuroprotective properties which are plausibly linked to astrocytic activity. © 2017 Elsevier B.V.

AUTHOR KEYWORDS: Astrocyte; Epilepsy; GLT-1 transporter; Glutamine synthetase; β-estradiol
INDEX KEYWORDS: 4 aminobutyric acid; estradiol; glutamate ammonia ligase; glutamic acid; lithium; pilocarpine; sodium glucose cotransporter 1; estradiol; excitatory amino acid transporter 2; glutamate ammonia ligase; pilocarpine; Slc1a2 protein, rat, animal experiment; animal model; animal tissue; anticonvulsant activity; Article; astrocyte; cell density; chronic drug administration; clonic seizure; controlled study; drug megadose; drug screening; enzyme activity; female; hippocampus; latent period; nerve cell excitability; neuroprotection; nonhuman; protein expression; rat; animal; astrocyte; body weight; chemically induced; disease model; dose response; drug effects; metabolism; nerve cell; pathology; Seizures; Wistar rat, Animals; Astrocytes; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Estradiol; Excitatory Amino Acid Transporter 2; Female; Glutamate-Ammonia Ligase; Hippocampus; Neurons; Pilocarpine; Rats; Rats, Wistar; Seizures

Sargolzehi, A., Abrari, K., Salmani, M.E., Goudarzi, I. Effects of melatonin on anxiety- like behaviors induced by post–traumatic stress disorder in rat (2016) Koomesh, 17 (2), pp. 479-485.

Introduction: Post traumatic stress disorder (PTSD) is an anxiety disorder. This study was aimed to evaluate the effect of multiple injections of melatonin on anxiety like behaviors induced by PTSD. Materials and methods: PTSD induced in 60 male wistar rats, by combining the shock and single-prolonged stress method (S&SPS). Animals received electric shock (1 mA, 2s) for 5 days, and then on the day 6 they underwent three stages of SPS (restrained for 2 hours, forced swimming for 20 minutes and anesthetized by diethyl ether for 15 minutes). Seven days after PTSD induction, elevated plus maze (EPM) and open field tests were performed to measure anxiety profile. Animals received multiple subcutaneous injections of melatonin (5, 10, 15 mg/kg) or saline, within the 7 days after PTSD. Results: The control (saline) and treated (melatonin) groups showed significant differences in the percentage of time spent in open arms of the EPM. Melatonin, at dose of 15mg/kg, significantly increased the time spent in open arms of the EPM than the corresponding control group. Animals who received 10mg/kg melatonin showed a significant increase in crossing behavior in open field test than the corresponding control group. Conclusion: Our study showed that melatonin is able to reduce PTSD-induced anxiety-like behaviors in rats. © 2015, Singapore Medical Association. All rights reserved.

AUTHOR KEYWORDS: Anxiety; Melatonin; Post-Traumatic Stress Disorder; Rats
INDEX KEYWORDS: melatonin, animal experiment; animal model; anxiety disorder; Article; controlled study; disease association; electric shock; elevated plus maze test; forced swim test; male; nonhuman; outcome assessment; posttraumatic stress disorder; rat

Mokhtarpour, M., Elahdadi Salmani, M., Lashkarbolouki, T., Abrari, K., Goudarzi, I. Lateral hypothalamus orexinergic system modulates the stress effect on pentylenetetrazol induced seizures through corticotropin releasing hormone receptor type 1 (2016) Neuropharmacology, 110, pp. 15-24.

DOI: 10.1016/j.neuropharm.2016.07.005

Stress is a trigger factor for seizure initiation which activates hypothalamic pituitary adrenal (HPA) axis as well other brain areas. In this respect, corticotropin releasing hormone (CRH) and lateral hypothalamus (LH) orexinergic system are involved in seizure occurrence. In this study, we investigated the role of LH area and orexin expression in (mediation of) stress effect on pentylenetetrazol (PTZ) -induced seizures with hippocampal involvement. Two mild foot shock stresses were applied to intact and adrenalectomized animals; with or without CRHr1 blocking (NBI 27914) in the LH area. Then, changes in orexin production were evaluated by RT-PCR. Intravenous PTZ infusion (25 mg/ml) -induced convulsions were scored upon modified Racine scale. Finally, hippocampal glutamate and GABA were evaluated to study excitability changes. We demonstrated that the duration and severity of convulsions in stress-induced as well as adrenalectomized group were increased. Plasma corticosterone (CRT) level and orexin mRNA expression were built up in the stress and/or seizure groups. Furthermore, glutamate and GABA content was increased and decreased respectively due to stress and seizures. In contrast, rats receiving CRHr1 inhibitor showed reduced severity and duration of seizures, increased GABA, decreased glutamate and corticosterone and also orexin mRNA compared to the inhibitor free rats. Stress and adrenalectomy induced augmenting effect on seizure severity and duration and the subsequent reduction due to CRHr1 blocking with parallel orexin mRNA changes, indicated the likely involvement of CRH1r induced orexin expression of the LH in gating stress effect on convulsions. © 2016 Elsevier Ltd

AUTHOR KEYWORDS: CRH; HPA axis; Orexin; PTZ; Seizure; Stress
INDEX KEYWORDS: 4 aminobutyric acid; corticosterone; corticotropin releasing factor receptor 1; glutamic acid; messenger RNA; orexin; pentetrazole; 2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine; aniline derivative; corticotropin releasing factor receptor; corticotropin releasing factor receptor 1; orexin; pentetrazole; pyrimidine derivative, adult; animal experiment; animal model; animal tissue; Article; blood level; brain function; brain region; controlled study; disease activity; disease association; disease duration; footshock; gene expression; lateral hypothalamus; male; molecular dynamics; molecular pathology; nonhuman; priority journal; protein determination; protein expression; protein function; rat; reverse transcription polymerase chain reaction; seizure; stress; animal; antagonists and inhibitors; biosynthesis; chemically induced; drug effects; lateral hypothalamus; mental stress; metabolism; prevention and control; psychology; seizure; Wistar rat, Aniline Compounds; Animals; Hypothalamic Area, Lateral; Male; Orexins; Pentylenetetrazole; Pyrimidines; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Seizures; Stress, Psychological

Ozbaki, J., Goudarzi, I., Salmani, M.E., Rashidy-Pour, A. Acute stress does not affect the impairing effect of chronic stress on memory retrieval (2016) Iranian Journal of Basic Medical Sciences, 19 (7), pp. 763-771.

DOI: 10.22038/ijbms.2016.7362

Objective(s): Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. Materials and Methods: Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. Results: Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. Conclusion: Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress. © 2016, Mashhad University of Medical Sciences. All rights reserved.

AUTHOR KEYWORDS: Acute stress; Chronic stress; Memory retrieval; Morris water maze; Rat
INDEX KEYWORDS: acute stress; adult; animal experiment; animal model; Article; chronic stress; controlled study; corticosterone blood level; enzyme linked immunosorbent assay; male; memory consolidation; memory disorder; Morris water maze test; nonhuman; rat

Bazrgar, M., Goudarzi, I., Lashkarbolouki, T., Elahdadi Salmani, M. Melatonin ameliorates oxidative damage induced by maternal lead exposure in rat pups (2015) Physiology and Behavior, 151, pp. 178-188.

DOI: 10.1016/j.physbeh.2015.06.040

During the particular period of cerebellum development, exposure to lead (Pb) decreases cerebellum growth and can result in selective loss of neurons. The detection and prevention of Pb toxicity is a major international public health priorities. This research study was conducted to evaluate the effects of melatonin, an effective antioxidant and free radical scavenger, on Pb induced neurotoxicity and oxidative stress in the cerebellum. Pb exposure was initiated on gestation day 5 with the addition of daily doses of 0.2% lead acetate to distilled drinking water and continues until weaning. Melatonin (10. mg/kg) was given once daily at the same time. 21. days after birth, several antioxidant enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed. Thiobarbituric acid reactive substance (TBARS) levels were measured as a marker of lipid peroxidation. Rotarod and locomotor activity tests were performed on postnatal days (PDs) 31-33 and a histological study was performed after completion of behavioral measurements on PD 33. The results of the present work demonstrated that Pb could induce lipid peroxidation, increase TBARS levels and decrease GPx and SOD activities in the rat cerebellum. We also observed that Pb impaired performance on the rotarod and locomotor activities of rats. However, treatment with melatonin significantly attenuated the motoric impairment and lipid peroxidation process and restored the levels of antioxidants. Histological analysis indicated that Pb could decrease Purkinje cell count and melatonin prevented this toxic effect. These results suggest that treatment with melatonin can improve motor deficits and oxidative stress by protecting the cerebellum against Pb toxicity. © 2015 Elsevier Inc.

AUTHOR KEYWORDS: Lead acetate; Melatonin; Oxidative stress; Purkinje cell; Rat
INDEX KEYWORDS: glutathione peroxidase; lead; melatonin; scavenger; superoxide dismutase; thiobarbituric acid reactive substance; glutathione peroxidase; lead; melatonin; neuroprotective agent; superoxide dismutase; thiobarbituric acid reactive substance, animal experiment; animal model; animal tissue; Article; cerebellum; controlled study; enzyme activity; experimental locomotor activity test; female; histopathology; lipid peroxidation; male; neuroprotection; neurotoxicity; nonhuman; oxidative stress; pregnancy; priority journal; rat; rotarod test; adverse effects; animal; drug effects; maternal exposure; metabolism; Movement Disorders; oxidative stress; pathology; pathophysiology; prenatal exposure; randomization; Wistar rat, Animals; Cerebellum; Female; Glutathione Peroxidase; Lead; Lipid Peroxidation; Maternal Exposure; Melatonin; Movement Disorders; Neuroprotective Agents; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Bagheri, F., Goudarzi, I., Lashkarbolouki, T., Elahdadi Salmani, M. Melatonin prevents oxidative damage induced by maternal ethanol administration and reduces homocysteine in the cerebellum of rat pups (2015) Behavioural Brain Research, 287, pp. 215-225.

DOI: 10.1016/j.bbr.2015.03.022

Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by animal experiments. This study was designed to evaluate the alterations in offspring rat cerebellum following increase of plasma Hcy level induced by maternal exposure to ethanol and to investigate the possible protective role of melatonin administration upon cerebellar ethanol-induced neurotoxicity. The adult female rats were divided randomly into 4 groups, including one control and three experimental groups, after vaginal plagues. Group I received normal saline, group II received ethanol (4. g/kg), group III received ethanol. +. melatonin (10. mg/kg) and group IV received melatonin on day 6 of gestation until weaning. 21 days after birth, plasma Hcy level, level of lipid peroxidation, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and levels of bcl-2 and bax mRNA expression in cerebellum were determined. Our results demonstrated that ethanol could induce lipid peroxidation, and decrease antioxidants activities and increase plasma total Hcy level. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rats. However, treatment with melatonin significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidant activities and significantly reduced plasma total Hcy levels. Moreover, melatonin reduced bax/bcl-2 ratio in the presence of ethanol. We conclude that these results provide evidence that ethanol neurotoxicity in part is related to increase of plasma Hcy levels and melatonin with reducing of plasma Hcy level has neuroprotective effects against ethanol toxicity in cerebellum. © 2015 Elsevier B.V.

AUTHOR KEYWORDS: Ethanol; Homocysteine; Melatonin; Oxidative stress; Purkinje cell; Rat
INDEX KEYWORDS: alcohol; catalase; glutathione peroxidase; homocysteine; melatonin; messenger RNA; protein Bax; protein bcl 2; sodium chloride; superoxide dismutase; thiobarbituric acid reactive substance; alcohol; Bax protein, rat; catalase; central depressant agent; glutathione peroxidase; homocysteine; melatonin; messenger RNA; neuroprotective agent; protein Bax; protein bcl 2; superoxide dismutase, adult; amino acid blood level; animal experiment; animal model; animal tissue; Article; cerebellum injury; cerebellum vermis; controlled study; drug effect; environmental exposure; enzyme activity; evening dosage; female; lipid peroxidation; locomotion; male; motor dysfunction; neuroprotection; neurotoxicity; nonhuman; oxidative stress; priority journal; protein expression; Purkinje cell; rat; rotarod test; animal; blood; cerebellum; drug effects; growth, development and aging; metabolism; oxidative stress; pathology; physiology; pregnancy; prenatal exposure; prevention and control; randomization; Wistar rat, Animals; bcl-2-Associated X Protein; Catalase; Central Nervous System Depressants; Cerebellum; Ethanol; Female; Glutathione Peroxidase; Homocysteine; Lipid Peroxidation; Locomotion; Melatonin; Neuroprotective Agents; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Rats, Wistar; RNA, Messenger; Superoxide Dismutase

Goudarzi, E., Elahdadi Salmani, M., Lashkarbolouki, T., Goudarzi, I. Hippocampal orexin receptors inactivation reduces PTZ induced seizures of male rats (2015) Pharmacology Biochemistry and Behavior, 130, pp. 77-83.

DOI: 10.1016/j.pbb.2015.01.006

Introduction Orexin has been shown to be involved in a number of physiological and behavioral processes including, feeding and metabolism, reward, nociception, and anxiety. Furthermore, orexin can cause increased neuronal excitability that gives rise to epileptic activity. The distribution of orexin receptor expression in the hippocampus, suggests a possible importance of orexin in the control of seizures in the temporal lobe epilepsy. Therefore, in this study, the effect of hippocampal orexin 1 and 2 receptors on seizure and glutamate and GABA (gamma-aminobutyric acid) contents was explored. Materials and methods Orexin 1 receptor (OX1R) antagonist (SB) and OX2R antagonist (TCS) were administrated bilaterally through separate cannulae into both hippocampi. Behavioral convulsions were provoked by intravenous pentylenetetrazol (PTZ) application model. The amount of total hippocampal glutamate and GABA contents was then measured by a biochemical method. Results SB (50 nmol) infusion reduced seizure stage, duration and decreased glutamate while GABA content was increased. SB (200 nmol) also reduced seizure stage, duration and glutamate content, without change of GABA content. TCS (20 nmol) infusion reduced seizure stage and duration without concomitant change in glutamate and GABA contents. Further, TCS (40 nmol) did neither affect the seizure nor the GABA, while decreased glutamate content. Co-administration of SB (50 nmol) with TCS (40 nmol) and also SB (200 nmol) with TCS (40 nmol) reduced seizure stage, duration and glutamate, but increased GABA content. Conclusion It is concluded that OX1R and OX2R antagonists reduce convulsive intensity, partially through alterations of hippocampal glutamate and GABA contents. © 2015 Elsevier Inc. All rights reserved.

AUTHOR KEYWORDS: GABA; Glutamate; Orexin receptor antagonist; Pentylenetetrazol; Seizures
INDEX KEYWORDS: 1 (2 methyl 6 benzoxazolyl) 3 (1,5 naphthyridin 4 yl)urea; 4 aminobutyric acid; agents interacting with transmitter, hormone or drug receptors; glutamic acid; orexin 1 receptor; orexin 2 receptor; orexin 2 receptor antagonist; unclassified drug; 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; 1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3,3-dimethyl-2-((4-pyridinylmethyl)amino)-1-butanone; 4 aminobutyric acid; benzoxazole derivative; convulsant agent; glutamic acid; isoquinoline derivative; orexin receptor; orexin receptor antagonist; pentetrazole; pyridine derivative; urea, animal experiment; animal model; Article; behavior assessment; clinical effectiveness; clinical evaluation; comparative study; controlled study; convulsion; disease duration; dose response; hippocampus; male; neuromodulation; neurotransmission; nonhuman; pentylenetetrazole-induced seizure; priority journal; protein determination; protein expression; rat; treatment duration; analogs and derivatives; animal; antagonists and inhibitors; chemically induced; drug effects; hippocampus; metabolism; microinjection; seizure, Rattus, Animals; Benzoxazoles; Convulsants; gamma-Aminobutyric Acid; Glutamic Acid; Hippocampus; Isoquinolines; Male; Microinjections; Orexin Receptor Antagonists; Orexin Receptors; Pentylenetetrazole; Pyridines; Rats; Seizures; Urea

Oladi, M., Nohtani, M., Avan, A., Mirhafez, S.R., Tajbakhsh, A., Ghasemi, F., Asadi, A., Elahdadi Salmani, M., Mohammadi, A., Hoseinzadeh, L., Ferns, G.A., Mobarhan, M.G. Impact of the C1431T polymorphism of the peroxisome proliferator activated receptor-gamma (PPAR-γ) gene on fasted serum lipid levels in patients with coronary artery disease (2015) Annals of Nutrition and Metabolism, 66 (2-3), pp. 149-154.

DOI: 10.1159/000381358

Background/Aims: The C1431T polymorphism of peroxisome proliferator activated receptor-γ (PPAR-γ) gene is related to diabetes and metabolic-syndrome. However, studies have been inconclusive about its association with coronary artery disease (CAD) and there have been no studies analyzing the association of this polymorphism with fasted-serum-lipid levels in Iranian-individuals with CAD. We investigated the association of PPAR-γ C1431T-polymorphism with CAD and dyslipidaemia in 787 individuals. Methods: Anthropometric-parameters and biochemical-measurements were evaluated, followed by genotyping. The association of the genetic-polymorphisms with CAD and lipid-profile was determined by univariate/multivariate-analyses. Results: Patients with CT or CT+TT genotype were at an increased-risk of CAD relative to CC-carriers (adjusted odds ratio: 2.03; 95% confidence interval, 1.01-4.09; p = 0.046). However, in the larger population, CT genotype was present at a higher frequency in the group with a positive angiogram. Furthermore, CT+TT genotypes were associated with an altered fasted-lipid-profile in the initial population sample of patients with a positive angiogram, compared to the group with a negative-angiogram. The angiogram-positive patients carrying the T allele had a significantly higher triglyceride, serum C-reactive protein and fasting-blood-glucose. Conclusion: We have found the PPAR-γ C1431T polymorphism was significantly associated with fasted serum lipid profile in individuals with angiographically defined CAD. Since accumulating data support the role of PPAR-γ polymorphisms in CAD, further studies are required to investigate the association of this polymorphism with coronary artery disease. © 2015 S. Karger AG, Basel.

AUTHOR KEYWORDS: Coronary artery disease; Lipid profile; PPAR-γ C1431T polymorphism
INDEX KEYWORDS: peroxisome proliferator activated receptor gamma; lipid; peroxisome proliferator activated receptor gamma, adult; angiography; anthropometric parameters; Article; controlled study; coronary artery disease; dyslipidemia; female; genotype; human; lipid blood level; major clinical study; male; measurement; priority journal; blood; coronary artery disease; cross-sectional study; diet restriction; genetic polymorphism; genetic predisposition; genetics; middle aged; odds ratio, Adult; Coronary Disease; Cross-Sectional Studies; Fasting; Female; Genetic Predisposition to Disease; Genotype; Humans; Lipids; Male; Middle Aged; Odds Ratio; Polymorphism, Genetic; PPAR gamma

Said Mohammadi, H., Goudarzi, I., Lashkarbolouki, T., Abrari, K., Elahdadi Salmani, M. Chronic administration of quercetin prevent spatial learning and memory deficits provoked by chronic stress in rats (2014) Behavioural Brain Research, 270, pp. 196-205.

DOI: 10.1016/j.bbr.2014.05.015

There are several reports that cognitive impairment is observed in stress related disorders and chronic stress impairs learning and memory. However, very few studies have looked into the possible ways of preventing this stress-induced deficit. This research study was conducted to evaluate the effects of quercetin, a natural flavonoid, with strong antioxidant and free radical scavenger properties, on chronic stress induced learning and memory deficits and oxidative stress in hippocampus. For chronic stress, rats were restrained daily for 6. h/day (from 9:00 to 15:00) for 21 days in well-ventilated plexiglass tubes without access to food and water. The animals were injected with quercetin or vehicle 60. min before restraint stress over a period of 21 days. Then, rats trained with six trials per day for 6 consecutive days in the water maze. On day 28, a probe test was done to measure memory retention. In addition, oxidative stress markers in the hippocampus were evaluated. Results of this study demonstrated that chronic stress exposure rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. Quercetin (50. mg/kg) treatment during restraint stress (21 days) markedly decreased escape latency and increased time spent in target quadrant during Morris water maze task. In comparison to vehicle treated group, chronic-stress group had significantly higher malondialdehyde (MDA) levels, significantly higher superoxide dismutase (SOD) activity and significantly lower glutathione peroxidase (GPx) activity in the hippocampus. Quercetin treatment caused a significant decrease in the hippocampus MDA levels and improves SOD and GPx activities in stressed animals. Finally, quercetin significantly decreased plasma corticosterone levels in stressed animals. Based on results of this study, chronic stress has detrimental effects on learning and memory and quercetin treatment can prevent from oxidative stress and impairment of learning and memory induced by chronic stress. © 2014 Elsevier B.V.

AUTHOR KEYWORDS: Chronic stress; Oxidative stress; Quercetin; Rat; Spatial memory
INDEX KEYWORDS: corticosterone; glutathione peroxidase; malonaldehyde; quercetin; superoxide dismutase; antioxidant; corticosterone; glutathione peroxidase; malonaldehyde; quercetin; superoxide dismutase, amnesia; analysis of variance; animal experiment; animal model; antioxidant activity; article; chronic stress; cognition; controlled study; corticosterone blood level; diet therapy; enzyme activity; hippocampus; immobilization stress; latent period; memory consolidation; Morris water maze test; neuroprotection; nonhuman; oxidative stress; priority journal; probe test; rat; spatial learning; training; animal; blood; complication; drug effects; exercise; male; maze test; Memory Disorders; mental stress; metabolism; neuropsychological test; procedures; psychology; spatial learning; spatial memory; time; treatment outcome; Wistar rat, Animals; Antioxidants; Corticosterone; Glutathione Peroxidase; Hippocampus; Male; Malondialdehyde; Maze Learning; Memory Disorders; Neuropsychological Tests; Quercetin; Rats; Rats, Wistar; Restraint, Physical; Spatial Learning; Spatial Memory; Stress, Psychological; Superoxide Dismutase; Time Factors; Treatment Outcome

Firozan, B., Goudarzi, I., Elahdadi Salmani, M., Lashkarbolouki, T., Rezaei, A., Abrari, K. Estradiol increases expression of the brain-derived neurotrophic factor after acute administration of ethanol in the neonatal rat cerebellum (2014) European Journal of Pharmacology, 732 (1), pp. 1-11.

DOI: 10.1016/j.ejphar.2014.02.041

Recently it has been shown that estradiol prevents the toxicity of ethanol in developing cerebellum. The neuroprotective effect of estradiol is not due to a single phenomenon but rather encompasses a spectrum of independent proccesses. According to the specific timing of Purkinje cell vulnerability to ethanol and several protective mechanisms of estradiol, we considered the neurotrophin system, as a regulator of differentiation, maturation and survival of neurons during CNS development. Interactions between estrogen and Brain derived neurotrophic factor (BDNF, an essential factor in neuronal survival) lead us to investigate involvement of BDNF pathway in neuroprotective effects of estrogen against ethanol toxicity. In this study, 17β-estradiol (300-900 μg/kg) was injected subcutaneously in postnatal day (PD) 4, 30 min prior to intraperitoneal injection of ethanol (6 g/kg) in rat pups. Eight hours after injection of ethanol, BDNF mRNA and protein levels were assayed. Behavioral studies, including rotarod and locomotor activity tests were performed in PD 21-23 and histological study was performed after completion of behavioral tests in PD 23. Our results indicated that estradiol increased BDNF mRNA and protein levels in the presence of ethanol. We also observed that pretreatment with estradiol significantly attenuated ethanol-induced motoric impairment. Histological analysis also demonstrated that estradiol prevented Purkinje cell loss following ethanol treatment. These results provide evidence on the possible mechanisms of estradiol neuroprotection against ethanol toxicity. © 2014 Elsevier B.V.

AUTHOR KEYWORDS: 17β-estradiol; Brain derived neurotrophic factor; Ethanol; Neuroprotection; Purkinje cell
INDEX KEYWORDS: alcohol; brain derived neurotrophic factor; complementary DNA; estradiol; messenger RNA; alcohol; brain derived neurotrophic factor; central depressant agent; estradiol; neuroprotective agent, alcohol blood level; animal behavior; animal tissue; article; cell loss; cerebellum; controlled study; DNA synthesis; drug mechanism; enzyme linked immunosorbent assay; experimental locomotor activity test; female; histology; male; motor dysfunction; neuroprotection; newborn; nonhuman; open field test; perinatal period; priority journal; protein expression; Purkinje cell; rat; reverse transcription polymerase chain reaction; RNA extraction; rotarod test; animal; blood; cerebellum; drug effects; metabolism; motor activity; pathology; psychomotor performance; signal transduction, Animals; Animals, Newborn; Brain-Derived Neurotrophic Factor; Central Nervous System Depressants; Cerebellum; Estradiol; Ethanol; Motor Activity; Neuroprotective Agents; Psychomotor Performance; Rats; Signal Transduction

Modir, F., Elahdadi Salmani, M., Goudarzi, I., Lashkarboluki, T., Abrari, K. Prenatal stress decreases spatial learning and memory retrieval of the adult male offspring of rats (2014) Physiology and Behavior, 129, pp. 104-109.

DOI: 10.1016/j.physbeh.2014.02.040

Introduction: Early life or prenatal stress induces many lifelong, mostly cognitive, homeostatic alterations in the behavior of the offspring. Purpose: We investigated the effect of heterogeneous sequential stress (HSS) at three separate periods, before and during the first and second half of pregnancies on spatial learning and memory retrieval of adult male offspring. Method: HSS is composed of several stressors, each in a day, during nine consecutive days including; restraint, swimming, isolation, and water and food deprivation on Wistar rats. The offspring were studied in a Morris water maze (MWM) apparatus to explore the latency, distance, proximity and target to opposite area as measures of learning and memory. Serum corticosterone was measured as a criterion of stress application. Results: HSS increased blood corticosterone in dams of PS2 (Pregnancy Stress second half), and also in adult male offspring from BPS (Before Pregnancy Stress) and PS1 (Pregnancy Stress first half) groups. The weight of the offspring decreased in the PS1 and PS2 groups. While distance traveled and latency to locate the hidden platform were increased in BPS and PS1 acquisition trials, swimming speed was unchanged during the acquisition and retrieval tests. Moreover, time to platform location was increased in BPS and PS1 during retention tests. While control rats spent more time in the target quadrant, stressed animals spent a longer duration in the opposite quadrant. Furthermore, proximity measure was increased in all stress treated rats. Conclusion: It is concluded that prenatal stress, around the beginning of the pregnancy, increases corticosterone in adult male offspring, which might be the basis for spatial learning and memory retrieval deficits in this study. © 2014 Elsevier Inc.

AUTHOR KEYWORDS: Adult offspring; Corticosterone; Learning and memory; Morris water maze; Prenatal stress
INDEX KEYWORDS: corticosterone; corticosterone, adult; animal experiment; article; birth weight; controlled study; corticosterone blood level; female; first trimester pregnancy; food deprivation; heterogeneous sequential stress; immobilization stress; latent period; learning; male; memory; Morris water maze test; nonhuman; prenatal stress; priority journal; progeny; rat; second trimester pregnancy; spatial learning; swimming; third trimester pregnancy; water deprivation; animal; blood; complication; Learning Disorders; maze test; Memory Disorders; mental stress; neuropsychological test; pregnancy; prenatal exposure; task performance; time; Wistar rat, Animals; Birth Weight; Corticosterone; Female; Learning Disorders; Male; Maze Learning; Memory Disorders; Neuropsychological Tests; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Wistar; Stress, Psychological; Swimming; Task Performance and Analysis; Time Factors

Shourmasti, F.R., Goudarzi, I., Abrari, K., Salmani, M.E., Laskarbolouki, T. Riluzole ameliorates harmaline-induced tremor in rat (2014) Basic and Clinical Neuroscience, 5 (2), pp. 138-143.

Introduction: Excessive olivo-cerebellar burst-firing occurs during harmaline-induced tremor. We hypothesized that antiglutamatergic agents would suppress harmaline tremor. From this point of view, the aim of the present study was to investigate the effects of riluzole on harmaline-induced tremor in rat. Methods: Four groups of Wistar rats weighing 80-100 g were injected with harmaline (30 mg/ kg i.p.) for inducing experimental tremors. The rats in group 1 served as control, whereas the animals in groups 2, 3 and 4 were also given riluzole intraperitonealy at doses of 2, 4 and 8 mg/ kg 30 min before and 90 min after harmaline administration. The onset latency, intensity and duration of tremor were recorded. Results: The results of this study demonstrated that riluzole could significantly increase latency period, and reduce duration and intensity of tremor. Discussion: It is concluded that pretreatment of riluzole can ameliorate harmaline-induced tremor in rats.

AUTHOR KEYWORDS: Harmaline; Rat; Riluzole; Tremor
INDEX KEYWORDS: harmaline; riluzole, animal experiment; animal model; article; controlled study; disease duration; disease severity; drug effect; drug efficacy; experimental study; latent period; male; nonhuman; rat; treatment response; tremor; Wistar rat

Paj, P., Salmani, M.E., Shajiee, H., Abiri, H., Goudarzi, I., Abrari, K. Stress during first pregnancy increases seizure threshold in adult male offspring (2014) Iranian Journal of Basic Medical Sciences, 17 (1), pp. 34-40.

Objective(s): Stress induces many homeostatic aberrations which are followed by lifelong allostatic responses. Epilepsy is developed or influenced by different environmental factors, i.e. prenatal stress which makes many contradictory developmental changes in seizure threshold and intensity. We investigated the potential seizure response of the rat offspring to prenatal stress; the stress which was applied to their mothers. Materials and Methods: Nine day heterogeneous sequential stress (HSS) model was used before and during the first and before the second pregnancy. The kindling was induced using 13 IP injections of pentylenetetrazol (PTZ) every 48 hr to adult male Wistar rat's offspring. Results: The results of the present study demonstrated that, before pregnancy stress decreased the rate of kindling (P<0.05) in the offspring, while stress which was applied during pregnancy completely prevented kindling (P <0.001). Further, their convulsive latency was increased and tonic clonic seizure duration was decreased. In contrast, previous pregnancy and between pregnancies stress could not change kindling process. Although maternal separation stress did not change kindling development, it could increase convulsive intensities by elongating the duration of seizures (P<0.05) and reducing convulsion latency (P <0.05). Conclusion: It is concluded that stress detrimental effects could be prevented by stress which was applied around first pregnancy; however this beneficial effect is weakened by before second pregnancy stress.


AUTHOR KEYWORDS: Kindling; Pentylenetetrazol; Pregnancy; Seizure; Stress
INDEX KEYWORDS: animal experiment; animal model; animal tissue; article; clonic seizure; controlled study; disease course; female; immobilization stress; kindling; male; nonhuman; pregnancy; rat; seizure threshold; stress; tonic clonic seizure

Alijan-Pour, J., Abrari, K., Lashkar Bluki, T., Ghorbanian, M.T., Goudarzi, I., Elahdadi Salmani, M., Mirshekar, M. Erratum: Acute ethanol administration affects memory reactivation: A look at the neuronal density and apoptosis in the rat hippocampus (Pharmacology Biochemistry and Behavior (2012) 102:2 (321 - 328)) (2014) Pharmacology Biochemistry and Behavior, 125, p. 85.

DOI: 10.1016/j.pbb.2014.05.020
INDEX KEYWORDS: Erratum; retracted article

Akbari, N., Salmani, M.E., Goudarzvand, M., Boluki, T.L., Goudarzi, I., Abrari, K. Unilateral hypothalamus inactivation prevents PTZ kindling development through hippocampal orexin receptor 1 modulation (2014) Basic and Clinical Neuroscience, 5 (1), pp. 66-73.

Introduction: Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA) inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard. Methods: Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R) blocking administered in CSF. Results: We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867) and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity. Discussion: It is concluded that LHA inactivation prevented kindling development probably through orexin receptor antagonism. CSF orexin probably acts as an inhibitory step on convulsive intensity through another unknown process.


AUTHOR KEYWORDS: Convulsion; Epileptogenesis; Kindling development; Orexinergic system; Pentylenetetrazol
INDEX KEYWORDS: 1 (2 methyl 6 benzoxazolyl) 3 (1,5 naphthyridin 4 yl)urea; glutamic acid; lidocaine; orexin 1 receptor; orexin A; pentetrazole, amino acid brain level; animal experiment; animal model; animal tissue; article; controlled study; convulsion; drug mechanism; drug receptor binding; hippocampus; hypothalamus; kindling; lateral hypothalamus; male; nerve excitability; neuromodulation; nonhuman; rat; receptor blocking; seizure

Ghasemi, M., Abrari, K., Goudarzi, I., Rashidy-Pour, A., Salmani, M.E. Effect of Cannabinoid Receptor Agonist WIN55, 212-2 on the Anxiety Induced By PTSD in Male Rats (2014) Physiology and Pharmacology, 18 (3), pp. 259-270.

Introduction: Posttraumatic stress disorder is a severe anxiety disorder caused by exposure to traumatic events. The aim of this study was to induce PTSD in rats and examine the effect of WIN55-212-2, a cannabinoid receptor agonist, on anxiety.
Methods: SPS&S model was used to induce PTSD in 56 male Wistar rats. Rats were restrained for 2 h, immediately followed by forced swimming for 20 min. After 15 min of recuperation, animals were exposed to diethyl ether until they lost consciousness. Thirty min later, rats received an electric foot shock in a shock chamber. Rats which were in the shock group, without experiencing SPS, only received an electrical foot shock. Animals received IP injections of WIN (two doses) or vehicle, before tests, in 3 continuous days. For PTSD induction, conditioned fear response was measured. Anxiety-like behavior was examined twice with elevated plus-maze.
Results: PTSD induction with SPS&S significantly decreased open arm time (OAT) and open arm entry (OAE) parameter, as compared to the control. WIN (0.25 mg/kg) significantly increased OAT as compared with the control.
Conclusion: WIN (0.25 mg/kg) decreased the anxiety like behavior induced by PTSD, so it seems to have antianxiety effect. © 2014, National Research Council of Canada. All rights reserved.


AUTHOR KEYWORDS: Anxiety; Cannabinoid receptors; Post-traumatic stress disorder; WIN55-212-2
INDEX KEYWORDS: cannabinoid receptor agonist; unclassified drug; win55-212-2, animal experiment; animal model; anxiety; Article; controlled study; electric shock; elevated plus maze test; fear; forced swim test; male; nonhuman; posttraumatic stress disorder; rat

Alijan-pour, J., Abrari, K., Bluki, T.L., Ghorbanian, M.T., Goudarzi, I., Salmani, M.E. Ethanol disrupts reactivated contextual conditioned fear memory: Behavioral and histological perspectives (2012) Cell Journal, 13 (4), pp. 265-274.

Objective: This research study is an attempt to examine whether the administration of ethanol after memory reactivation would modulate subsequent expression of memory in rats. Additionally, we examined whether this administration alters the density of Cornu Ammonis (CA)1 and CA3 pyramidal and dentate gyrus (DG) granule cells. Materials and Methods: In this experimental study, adult male Wistar rats (200-300 g) were trained in a fear conditioning system using two 1 second, 0.6 mA shocks with an interval of 180 seconds. Twenty four hours later rats were returned to the chamber for 120 seconds. Immediately after reactivation they were injected with ethanol (0.5, 1, 1.5 mg/kg) or saline. 1, 7 and 14 days after reactivation, rats were returned to the context for 5 minutes. Seconds of freezing (absence of all movement except respiration) were scored. In the second experiment (described in the previous paragraph), after test 1, animals were anesthetized with sodium pentobarbital and perfused transcardially with phosphate buffer (10 minutes) and 4% paraformaldehyde (15 minutes). The brains were postfixed in phosphate-buffered 4% paraformaldehyde (24 hours) and 30% sucrose. 10-μm sections were stained with cresyl violet. Data were analyzed by 1-and 2-way ANOVA for repeated measurements by means of SPSS 16.0. Tukey's post hoc test was performed to determine the source of detected significant differences. P <0.05 were considered significant. Data are presented as mean ± SEM. Results: Findings from the first experiment indicated that ethanol at a dose of 1.5 mg/kg significantly impaired recall of memory only in the first test. The density of CA1 and CA3 pyramidal and DG granule cells in the ethanol group was decreased (p< 0.01) compared with control group respectively 43.7%, 35.8%, and 37.8. Conclusion: The data demonstrate that ethanol exposure impairs post retrieval processes. Moreover, ethanol decreases the density of CA1, CA3 and DG cells. Presumably it would be a correlation between our behavioral and histological results.


AUTHOR KEYWORDS: Conditioning; Ethanol; Hippocampus; Reconsolidation
INDEX KEYWORDS: alcohol; paraformaldehyde; pentobarbital; phosphate buffered saline, analysis of variance; animal cell; animal experiment; animal model; animal tissue; article; behavior; clinical examination; conditioning; controlled study; dentate gyrus; experimental study; fear; granule cell; hippocampal CA1 region; hippocampal CA3 region; histology; male; medical research; memory; nonhuman; perfusion; rat

Rahimi Shourmasti, F., Goudarzi, I., Lashkarbolouki, T., Abrari, K., Elahdadi Salmani, M., Goudarzi, A. Effects of riluzole on harmaline induced tremor and ataxia in rats: Biochemical, histological and behavioral studies (2012) European Journal of Pharmacology, 695 (1-3), pp. 40-47.

DOI: 10.1016/j.ejphar.2012.08.014

Essential tremor (ET) is one of the most common and most disabling movement disorders among adults. The drug treatment of essential tremor remains unsatisfactory. Additional therapies are required for patients with inadequate response or intolerable side effects. Thus, we aimed to investigate the therapeutic effects of riluzole on harmaline-induced tremor and ataxia in rat, and determining whether riluzole exerts its effect through modulation of glutamate levels in cerebellum. The study included 5 groups of Wistar rats weighing 80-100 g, injected with harmaline (50 mg/kg i.p.) for inducing experimental tremors and ataxia. The rats in group 1 served as control (saline induced) and group 2 received harmaline alone, whereas the animals in groups 3, 4 and 5, were also given riluzole intraperitoneally at doses of 2, 4 and 8 mg/kg 10 min after harmaline administration, respectively. The intensity and duration of tremor were recorded. Rotarod test, distance traveled and number of crossings were used to evaluate motor performance. Results of this study demonstrated that riluzole dose dependently attenuated duration and intensity of harmaline-induced tremors. Also, riluzole significantly improves time to fall, distance traveled and number of crossings in combined riluzole and harmaline treated rats. Histological analysis indicated that harmaline could cause vermis Purkinje cell (PC) loss and riluzole prevented this toxic effect. Harmaline also could increase glutamate levels in vermis and treatment with riluzole restored glutamate levels. In conclusion, riluzole has relatively protective effects on harmaline-induced tremor, probably related to its inhibitory effect on glutamatergic neurotransmission. © 2012 Elsevier B.V. All rights reserved.


AUTHOR KEYWORDS: (Rat); Cerebellum; Harmaline; Riluzole; Tremor
INDEX KEYWORDS: riluzole, animal behavior; animal experiment; animal model; animal tissue; article; ataxia; cerebellum; controlled study; dose response; drug dose comparison; drug effect; histopathology; motor performance; neuromodulation; neuroprotection; neurotransmission; nonhuman; open field test; priority journal; Purkinje cell; rat; rotarod test; tremor, Animals; Ataxia; Behavior, Animal; Cerebellum; Glutamates; Harmaline; Ion Channels; Male; Neuroprotective Agents; Rats; Rats, Wistar; Riluzole; Rotarod Performance Test; Time Factors; Tremor

Alijan-Pour, J., Abrari, K., Bluki, T.L., Ghorbanian, M.T., Goudarzi, I., Salmani, M.E., Mirshekar, M. Acute ethanol administration affects memory reactivation: A look at the neuronal density and apoptosis in the rat hippocampus (2012) Pharmacology Biochemistry and Behavior, 102 (2), pp. 321-328.

DOI: 10.1016/j.pbb.2012.04.008

This study is an attempt to examine whether administration of ethanol after memory reactivation will modulate expression of memory in rats or not. We further examined whether this administration alters the number of tunnel positive cells in hippocampus. Adult male Wistar rats were trained in a fear conditioning system using two 1 s , 0.6 mA shock with an interval of 180 s. 24 h later the rats were returned to the chamber for reactivation, and then they were injected with ethanol (0.5, 1, 1.5 mg/kg) or saline, ip. Again, one, seven and fourteen days after reactivation, the rats were returned to the context for 5 min. The freezing time (absence of all movements except respiration) was scored in seconds. In the second experiment, after test 1, the animals were anesthetized and a transcardial perfuse with phosphate buffer and paraformaldehyde 4% was conducted. After post-fixation of brains 5-μm sections were stained with cresyl violet. Finally, paraffin-embedded sections of 10 μm were cut out throughout the tissue and each sample was processed with TUNEL. The number of apoptotic cells in a 130 μm-long segment of the hippocampal CA1 and CA3 fields and dentate gyrus was counted. The data demonstrate that ethanol exposure impairs post retrieval processes. Rats receiving ethanol (1.5 mg/kg) showed lower freezing levels during the first test. Moreover, ethanol decreases the density of CA1, CA3 and DG cells and increases the density of apoptotic cells in all regions of hippocampus. Therefore, ethanol exposure impairs reconsolidation of contextual fear conditioning probably via decreasing the density of CA1, CA3 and DG cells. © 2012 Elsevier Inc. All rights reserved.

AUTHOR KEYWORDS: Contextual fear conditioning; Ethanol; Hippocampus; Reconsolidation
INDEX KEYWORDS: alcohol; paraformaldehyde; phosphate buffered saline, acute drug administration; animal cell; animal experiment; animal tissue; apoptosis; article; cell density; controlled study; dentate gyrus; drug effect; freezing; hippocampal CA1 region; hippocampal CA3 region; hippocampus; male; memory; nerve cell; nick end labeling; nonhuman; priority journal; rat; tissue fixation; tissue section, Animals; Apoptosis; Behavior, Animal; Ethanol; Hippocampus; Male; Memory; Neurons; Rats; Rats, Wistar, Animalia; Rattus; Rattus norvegicus

Ramezani, A., Goudarzi, I., Lashkarboluki, T., Ghorbanian, M.T., Abrari, K., Salmani, M.E. Role of oxidative stress in ethanol-induced neurotoxicity in the developing cerebellum (2012) Iranian Journal of Basic Medical Sciences, 15 (4), pp. 965-974.

Objective(s): The purpose of this study was to investigate the role of oxidative stress in Purkinje cell neurotoxicity of ethanol-treated rat. Materials and Methods: Male rat pups 4-day-old was used in this study. Ethanol was administered to rat pups at a dose of 6 g/kg from postnatal days (PDs) 4 to 5. Pups were killed 90 min after the second alcohol treatment on PD 5 by decapitation and the brain was immediately removed. The cerebellum was dissected for analyzing the oxidative stress parameters and histological study. The activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in vermis of cerebellum were assayed. Thiobarbituric acid reactive substances (TBARS) levels were also measured as a marker of lipid peroxidation. Results: Administration of ethanol significantly increased TBARS levels in the cerebellum compared to control pups (P< 0.01). The treated pups with ethanol exhibited a marked decrease in the GPx activity (P< 0.01) whereas, in spite of decrease in the activities of SOD and CAT, when compared to control, there were not significant differences. The spherical cell bodies of Purkinje cells in control rats are aligned nicely between the granular and molecular layers. In ethanol treated pups, Purkinje cells scattered within the Purkinje cell layer and shrinkage of the cell somata is seen. Conclusion: The results of the present work demonstrated that ethanol exposure during the vulnerable window could increase TBARS levels (lipid peroxidation) and decrease GPx levels in pup's cerebellum. Also, the results confirmed ethanol-induced microencephaly, cerebellar Purkinje cell loss. These findings suggest that Purkinje cell loss is, in part through decrease in the activity of GPx and increase of lipid peroxidation in the rat cerebellum.


AUTHOR KEYWORDS: Cerebellum; Ethanol; Oxidative stress; Purkinje cell; Rat
INDEX KEYWORDS: alcohol; catalase; glutathione peroxidase; superoxide dismutase; thiobarbituric acid reactive substance, animal experiment; animal model; animal tissue; antioxidant activity; article; brain development; cerebellum vermis; controlled study; enzyme activity; histopathology; lipid peroxidation; male; microcephaly; neurotoxicity; newborn; nonhuman; oxidative stress; Purkinje cell; rat, Rattus

Azhdari-Zarmehri, H., Erami, E., Ghasemi, E., Elahdadi Salmani, M. Chronic heterogeneous sequential stress increases formalin-induced nociceptive behaviour in male rats (2012) Physiology and Pharmacology, 16 (4), pp. 371-379.

Introduction: Chronic heterogeneous stress may be better for evaluation of the effect of chronic stress situations on the nociceptive behaviour. The present study investigated the effects of chronic heterogeneous sequential stress on thermal-induced nociception and formalin induced pain behavior in rats. Methods: In the present study, adult rats (220-300 g) were used. Animals were divided in stressed and non-stressed groups. Heterogeneous sequential stress including food deprivation, water deprivation, restraint, restraint at room temperature, restraint at 4° C, forced swimming and social isolation stress. Formalin and hot-plate tests were used as chemical and thermal pain model effects in rats, respectively. Results: While non-stressed animals gained weight during the experiments, stressed rats lost their weight. Chronic heterogeneous sequential stress significantly increased latency to hot-plate test when compared to control, while it increased the nociceptive behaviour in phase 2 of formalin test in male rats compared to control ones. Conclusion: The model of chronic heterogeneous sequential stress presented here may be useful in evaluating the basic mechanisms linking stress and pain and suggest a method to assess the potential therapeutic efficacy of drugs targeting painful disorders with a strong stress component.


AUTHOR KEYWORDS: Chronic heterogeneous stress; Formalin test; Hot-plate; Pain; Rat
INDEX KEYWORDS: formaldehyde, animal experiment; article; chronic heterogeneous stress; controlled study; food deprivation; forced swim test; hot plate test; immobilization stress; male; nociception; nociceptive pain; nonhuman; rat; social isolation; stress; water deprivation

Ramezani, A., Goudarzi, I., Lashkarbolouki, T., Ghorbanian, M.T., Elahdadi Salmani, M., Abrari, K. Neuroprotective effects of the 17β-estradiol against ethanol-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: Biochemical, histological and behavioral changes (2011) Pharmacology Biochemistry and Behavior, 100 (1), pp. 144-151.

DOI: 10.1016/j.pbb.2011.07.010

During particular periods of central nervous system (CNS) development, exposure to ethanol can decrease regional brain growth and can result in selective loss of neurons. Unfortunately, there are few effective means of attenuating damage in the immature brain. In this study, the possible antioxidant and neuroprotective properties of 17β-estradiol against ethanol-induced neurotoxicity was investigated. 17β-estradiol (600 μg/kg) was injected subcutaneously in postnatal day (PD) 4 and 5, 30 min prior to intraperitoneal injection of ethanol (6 g/kg) in rat pups. Ninety minutes after injection of ethanol, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (Gpx) in vermis of cerebellum were assayed. Thiobarbituric acid reactive substance (TBARS) levels were also measured as a marker of lipid peroxidation. Behavioral studies, including rotarod and locomotor activity tests were performed in PD 21-23 and histological study was performed after completion of behavioral measurements in postnatal day 23. The results of the present work demonstrated that ethanol could induce lipid peroxidation, increase TBARS levels and decrease glutathione peroxidase levels in pup cerebellum. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rat pups. However, treatment with 17β-estradiol significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidants. Histological analysis also indicated that ethanol could decrease vermis Purkinje cell count and 17β-estradiol prevented this toxic effect. These results suggest that ethanol may induce lipid peroxidation in the rat pups cerebellum while treatment with 17β-estradiol improves motor deficits by protecting the cerebellum against ethanol toxicity. © 2011 Elsevier Inc.


AUTHOR KEYWORDS: 17β-estradiol; Ethanol; Lipid peroxidation; Oxidative stress; Purkinje cell; Rat pups
INDEX KEYWORDS: alcohol; catalase; estradiol; glutathione peroxidase; superoxide dismutase; thiobarbituric acid reactive substance, animal experiment; antioxidant activity; article; behavior change; biochemistry; brain development; cerebellum; cerebellum vermis; controlled study; female; histology; locomotion; male; neuroprotection; neurotoxicity; nonhuman; oxidative stress; perinatal period; priority journal; Purkinje cell; rat; rotarod test; task performance, Animals; Animals, Newborn; Cerebellum; Estradiol; Ethanol; Male; Motor Activity; Motor Skills Disorders; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar, Rattus

Salmani, M.E., Fathollahi, Y., Mirnajafizadeh, J., Semnanian, S. Epileptogenic insult alters endogenous adenosine control on long-term changes in synaptic strength by theta pattern stimulation in hippocampus area CA1 (2011) Synapse, 65 (3), pp. 189-197.

DOI: 10.1002/syn.20834

The impact of theta patterning of the stimulation on the kindling effects of pentylenetetrazol (PTZ) was studied in rat hippocampus area CA1 in vitro. A potential involvement of adenosine A1 receptors was also examined. Primed-bursts stimulation (PBs) and theta pulse stimulation (TPS) were used as patterned activities. Stimulus patterns were applied to the Schaffer collateral afferents of hippocampal slices from both control and PTZ-kindled rats, the field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) were simultaneously recorded from stratum radiatum and stratum pyramidale, respectively. Experiments were carried out in the presence or absence of the adenosine A1 receptor antagonist CPX. The following changes in kindled vs. control slices were observed. PBs was unable to produce both fEPSP LTP and PS LTP in untreated slices. When A1 receptor antagonist CPX was applied before PBs, both fEPSP LTP and PS LTP were elicited. PS LTP was selectively depressed by TPS (applied at 60 min after LTP induction) exclusively when A1 receptors were blocked, while TPS failed to depress PS LTP in untreated PBs-exposed slices. These findings suggest that seizing entails lasting changes in hippocampus area CA1 so that LTP induction by PBs is masked due to intensive adenosine release which in turn prevents TPS to induce PS LTD in epileptic CA1 network. © 2010 Wiley-Liss, Inc.


AUTHOR KEYWORDS: CA1 neural network; Epileptogenic insult; Primed burst stimulation; Synaptic plasticity; Theta pulse stimulation
INDEX KEYWORDS: adenosine; adenosine A1 receptor; pentetrazole, animal experiment; animal model; article; controlled study; epilepsy; epileptic focus; excitatory postsynaptic potential; hippocampal CA1 region; hippocampus theta rhythm; in vitro study; male; nonhuman; pattern stimulation; priority journal; pulse rate; rat; stimulation; stratum pyramidale; stratum radiatum

Goudarzi, I., Hajizadeh, S., Salmani, M.E., Abrari, K. Pulsed electromagnetic fields accelerate wound healing in the skin of diabetic rats (2010) Bioelectromagnetics, 31 (4), pp. 318-323.

DOI: 10.1002/bem.20567

Delayed wound healing is a common complication in diabetes mellitus. From this point of view, the main purpose of the present study is to investigate the effect of extremely low frequency pulsed electromagnetic fields (ELF PEMFs) on skin wound healing in diabetic rats. In this study, diabetes was induced in male Wistar rats via a single subcutaneous injection of 65 mg/kg streptozocin (freshly dissolved in sterile saline, 0.9%). One month after the induction of diabetes, a full-thickness dermal incision (35 mm length) was made on the right side of the paravertebral region. The wound was exposed to ELF PEMF (20 Hz, 4 ms, 8 mT) for 1 h per day. Wound healing was evaluated by measuring surface area, percentage of healing, duration of healing, and wound tensile strength. Obtained results showed that the duration of wound healing in diabetic rats in comparison with the control group was significantly increased. In contrast, the rate of healing in diabetic rats receiving PEMF was significantly greater than in the diabetic control group. The wound tensile strength also was significantly greater than the control animals. In addition, the duration of wound healing in the control group receiving PEMF was less than the sham group. Based on the above-mentioned results we concluded that this study provides some evidence to support the use of ELF PEMFs to accelerate diabetic wound healing. Further research is needed to determine the PEMF mechanisms in acceleration of wound healing in diabetic rats. © 2010 Wiley-Liss, Inc.


AUTHOR KEYWORDS: Diabetes; Pulsed electromagnetic field; Rat; Streptozocin; Wound healing
INDEX KEYWORDS: Animalia; Rattus; Rattus norvegicus, streptozocin, animal; article; electromagnetic field; experimental diabetes mellitus; injury; male; pathophysiology; radiation exposure; rat; skin; tensile strength; Wistar rat; wound healing, Animals; Diabetes Mellitus, Experimental; Electromagnetic Fields; Male; Rats; Rats, Wistar; Skin; Streptozocin; Tensile Strength; Wound Healing

Jafarzadeh, Z., Fathollahi, Y., Semnanian, S., Omrani, A., Salmanzadeh, F., Salmani, M.E. Morphine dependence increases the response to a brief pentylenetetrazol administration in rat hippocampal CA1 in vitro (2009) Epilepsia, 50 (4), pp. 789-800.

DOI: 10.1111/j.1528-1167.2008.01802.x

Purpose: Herein we used electrophysiologic approaches in hippocampal area CA1 to estimate how morphine treatment alters the pentylenetetrazol (PTZ) effects. Methods: Hippocampal slices taken from either control animals or animals made dependent via chronic morphine administration were examined. Changes in the population spike and epileptiform amplitudes were used as indices to quantify the effects of PTZ exposure in the control and morphine-dependent slices. Hippocampal slices taken either from control animals or from animals made dependent upon morphine were exposed to PTZ, either with or without morphine, naloxone, or morphine + naloxone. Results: Morphine dependence increased a PTZ-induced long-term potentiation (LTP) of the population spike in CA1 in vitro. This LTP was not found in rats that had spontaneously withdrawn morphine or withdrawn with naloxone in vivo after chronic morphine intake. Morphine or naloxone in vitro blocked the PTZ-induced LTP changes in control and morphine-dependent slices. However, PTZ-induced multiple population spikes (epileptiform activity) in CA1 was not blocked by naloxone. Discussion: It is concluded that dependence on morphine enhances PTZ-induced plastic and epileptic changes in CA1 excitability. We suggest that this model of neuronal activity in dependent slices could present an opportunity for studying the mechanisms underlying the increased likelihood of seizures in morphine users. © 2008 International League Against Epilepsy.


AUTHOR KEYWORDS: Addiction; CA1 neural network; Long-term depression; Long-term potentiation; Seizure; Synaptic plasticity
INDEX KEYWORDS: morphine; naloxone; pentetrazole, animal experiment; animal model; animal tissue; article; brain electrophysiology; controlled study; epilepsy; epileptic discharge; hippocampus; in vitro selection; male; morphine addiction; nerve cell plasticity; nonhuman; priority journal; rat; spike wave, Animals; Convulsants; Disease Models, Animal; Drug Interactions; Electric Stimulation; Evoked Potentials; Hippocampus; Long-Term Potentiation; Male; Morphine; Morphine Dependence; Naloxone; Narcotic Antagonists; Narcotics; Neural Pathways; Pentylenetetrazole; Rats; Rats, Inbred Strains; Statistics, Nonparametric; Substance Withdrawal Syndrome

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