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A review on the roles of electrical low-frequency deep brain stimulation and modulatory action of the serotonergic system in seizure 2 2 Epilepsy is a common neurological disorder that affects approximately 50 million people and about 30% of them have seizures despite antiepileptic-drug therapy. Even if 50% of these 600,000 or so patients benefit from surgical resection, many would still need new therapeutic approaches. Deep brain stimulation (DBS) has been suggested as an alternative to drug therapy. Low frequency stimulation (LFS) is an effective pattern of DBS that can decrease epileptic seizures. The incidence of epileptic seizures has been described by an imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission. This phenomenon may be affected by other neurotransmitter systems, including serotonin (5-hydroxytryptamine, 5-HT). The Serotonergic system undergoes many alterations in the epileptic brain. The link between LFS and serotonin release has been studied and it is documented that 5- HT1A receptor antagonist reduces the anti-convulsant effects of LFS. Thus, considering the effects of the serotonergic system in neuronal activities in the epileptic brain, it may be involved in the anti-convulsant mechanism(s) of LFS. In this review, we introduce the effects of low frequency stimulation on seizure and its possible mechanisms. The role of some neuromodulators in mediating the anti-convulsive effects of LFS and the probable signaling changes will be discussed. 235 248 2019/05/11 1398/2/21 2019/08/3 1398/5/12 Alireza Gharib Alireza Gharib Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Iran Amir Shojaie Amir Shojaie Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Iran Meysam Zare Meysam Zare Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Iran Alireza Komaki Alireza Komaki Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Iran Abdolrahman Sarihi Abdolrahman Sarihi Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Iran sarihi@umsha.ac.ir Epilepsy Low frequency stimulation Neuromodulator. Albensi BC, Ata G, Schmidt E, Waterman JD, Janigro D. 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Oxidative stress, nitric oxide and inflammation in the pathophysiology of varicocele and the effect of hydrogen sulfide as a potential treatment 2 2 Varicocele is defined as the non-palpable enlargement of the spermatic venous plexus, which has implications on the sperm quality and fertility. The guidelines for managing varicocele in adolescents are not fully determined yet. However, based on the recent reports, during varicocele injuries to testicular tissues may be a result of the formation of reactive oxygen species (ROS) and the subsequent oxidative damage. The testis has a high metabolism rate and cell replication which itself causes excessive production of the ROS and decreases antioxidant capacity. Massive generation of ROS and their interaction with lipids, proteins and nucleic acids has adverse effects on the normal cell function. This review article describes the varicocele, its etiology, pathophysiological mechanisms and current treatment methods. An electronic search has been conducted, during 2018, via PubMed and Medline database English literature. Peer-reviewed articles were targeted and the following key-words were used: varicocele, diagnosis, etiology, cellular and molecular mechanisms. Available full-text articles were read. Related articles were also scrutinized. A hand search was also driven. Taken together, this review article mention three main pathophysiology of varicocele that can be treated by natural antioxidant. In addition, hydrogen sulfide as another factor was discussed because the reduction of this substance contribute to the male infertility which induce by varicocele. 249 260 2019/05/112019/03/4 1397/12/13 2019/08/32019/07/23 1398/5/1 Keivan Lorian Keivan Lorian Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran Mehri Kadkhodaee Mehri Kadkhodaee Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran Farzaneh Kianian Farzaneh Kianian Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran Arash Abdi Arash Abdi Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran Hamidreza Sadeghipour Hamidreza Sadeghipour Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran Behjat Seifi Behjat Seifi Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Iran b-seifi@tums.ac.ir Varicocele Diagnosis Etiology Cellular and molecular mechanisms. 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The role of S100B and nitric oxide in the apoptotic action of pentylenetetrazole on astrocytes 2 2 Introduction: Astrocyte, S100B and nitric oxide may have a role in the pathogenesis and treatment of epilepsy. However, the effects of nitric oxide and S100B on the gliotoxic effects of chemical convulsants such as pentylenetetrazole (PTZ) is unknown. Therefore, we aimed to evaluate the effects of S100B and nitric oxide on gliotoxicity of PTZ in a 1321NI1 astrocytic culture. Methods: The 1321N1 astrocytes were exposed to PTZ (40mM), arundic acid (50μM) or both of them for 24h. In addition, we poured L-arginine (100 or 500μM), N-nitro-L-arginine methyl ester (100 or 500μM), 7-nitroindazole (30 or 100μM) and aminoguanidine (50 or 100μM) to the culture media contained PTZ, arundic acid or both of them and incubated for 24h. Cell viability was measured by the methylthiazolyldiphenyl-tetrazolium bromide reagent and the S100B protein level was measured using an enzyme-linked immunosorbent assay. Results: There was a negative correlation between cell viability in astrocytes and the intracellular S100B levels. PTZ decreased cell viability, but it increased the intracellular S100B levels. Arundic acid, N-nitroarginine methyl ester, 7-nitroindazole and aminoguanidine reversed the PTZ effects on cell viability and intracellular S100B levels. Adding the L-arginine to PTZ plus arundic acid reduced the modulatory effects of arundic acid on PTZ. Conclusion: Nitric oxide and S100B have a role in gliotoxicity of PTZ in cell culture. Arundic acid suppresses PTZ-induced S100B elevation and gliotoxicity possibly by modulation of the nitric oxide pathway. 261 269 2019/05/112019/03/42019/01/6 1397/10/16 2019/08/32019/07/232019/06/18 1398/3/28 Mojtaba Keshavarz Mojtaba Keshavarz Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Iran mkeshavar@sums.ac.ir Atena Amiri Atena Amiri Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Iran Arundic acid Astrocytes Nitric oxide Pentylenetetrazole S100 Calcium Binding Protein beta Subunit. Banach M, Piskorska B, Czuczwar SJ, Borowicz KK. Nitric oxide, epileptic seizures, and action of antiepileptic drugs. CNS Neurol Disord Drug Targets 2011; 10: 808-19.##Devinsky O, Vezzani A, Najjar S, De Lanerolle NC, Rogawski MA. Glia and epilepsy: excitability and inflammation. Trends Neurosci 2013; 36: 174-84.##Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, et al. S100B's double life: intracellular regulator and extracellular signal. Biochim Biophys Acta 2009; 1793: 1008-22.##Efremova L, Schildknecht S, Adam M, Pape R, Gutbier S, Hanf B, et al. Prevention of the degeneration of human dopaminergic neurons in an astrocyte co-culture system allowing endogenous drug metabolism. Br J Pharmacol 2015; 172: 4119-32.##Eloqayli H, Dahl CB, Götestam KG, Unsgård G, Hadidi H, Sonnewald U. Pentylenetetrazole decreases metabolic glutamate turnover in rat brain. J Neurochem 2003; 85: 1200-7.##Eloqayli H, Dahl CB, Götestam KG, Unsgård G, Sonnewald U. Changes of glial–neuronal interaction and metabolism after a subconvulsive dose of pentylenetetrazole. Neurochem Int 2004; 45: 739-45.##Fernandes RA, Ingle AB. Arundic acid a potential neuroprotective agent: biological development and syntheses. Curr Med Chem 2013; 20: 2315-29.##Garry PS, Ezra M, Rowland MJ, Westbrook J, Pattinson KTS. The role of the nitric oxide pathway in brain injury and its treatment--from bench to bedside. Exp Neurol 2015; 263: 235-43.##Griffin WS, Yeralan O, Sheng JG, Boop FA, Mrak RE, Rovnaghi CR, et al. Overexpression of the neurotrophic cytokine S100 beta in human temporal lobe epilepsy. J Neurochem 1995; 65: 228-33.##Gupta S, Goswami P, Biswas J, Joshi N, Sharma S, Nath C, et al. 6-Hydroxydopamine and lipopolysaccharides induced DNA damage in astrocytes: involvement of nitric oxide and mitochondria. Mutat Res Genet Toxicol Environ Mutagen 2015; 778: 22-36.##Hewett SJ, Csernansky CA, Choi DW. Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS. Neuron 1994; 13: 487-94.##Hu J, Castets F, Guevara JL, Van Eldik LJ. S100β stimulates inducible nitric oxide synthase activity and mrna levels in rat cortical astrocytes. J Biol Chem 1996; 271: 2543-7.##Hu J, Ferreira A, Van Eldik LJ. 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In: Antiepileptic Drugs. Ohio: Springer, 1999, p. 19-62.##Macdonald RL, Barker JL. Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian neurons. Science 1978; 200: 775-7.##Meng XJ, Wang F, Li CK. Resveratrol is neuroprotective and improves cognition in pentylenetetrazole-kindling model of epilepsy in rats. Indian J Pharm Sci 2014; 76: 125-31.##Mrak RE, Griffinb WS. The role of activated astrocytes and of the neurotrophic cytokine S100B in the pathogenesis of Alzheimer's disease. Neurobiol Aging 2001; 22: 915-22.##Qu H, Eloqayli H, Sonnewald U. Pentylenetetrazole affects metabolism of astrocytes in culture. J Neurosci Res 2005; 79: 48-54.##Quintas C, Pinho D, Pereira C, Saraiva L, Gonçalves J, Queiroz G. Microglia P2Y 6 receptors mediate nitric oxide release and astrocyte apoptosis. J Neuroinflamm 2014; 11: 141.##Sen J, Belli A. S100B in neuropathologic states: the CRP of the brain?. 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Pre-gestational feeding of thymoquinone suppressed pentylenetetrazole-induced generalized seizure while potentiated focal seizure in rat offspring 2 2 Introduction: Pre-gestational nutrition, before and during pregnancy, might play a key role in nervous system. This study aimed to investigate effect of pre-gestational administration of thymoquinone (TQ) on pentylenetetrazole (PTZ)-induced seizure in rat offspring. Methods: Thirty-two female Wistar rats were divided to four groups (n=8) as follows: 1-control (received one ml ethanol 25% by gavage for seven constitutive days), 2-TQ10, 3-TQ 40 and 4-TQ 80. The rats in the groups 2, 3 and 4 received 10, 40 and 80mg/kg TQ dissolved in one ml ethanol 25% by gavage for seven constitutive days, respectively. The day after finishing the TQ administration, each female rat was mated with a sexually experienced male rat. The pregnant rats were housed in groups of four per cage until the day 20 of gestation. Then, the rats were individually transferred to a separate cage and the same conditions were applied for all of them. After parturition, the pups were counted, weighed and culled to eight in each litter. On postnatal day 14 (P14) and P21, the pups were subjected to PTZ-induced seizure. Results: Latency of the first seizure decreased in the TQ40 and TQ80 groups and the duration of focal seizure increased both at P14 and P21. The progress of seizure stages and duration of tonic-clonic seizures were suppressed in TQ-treated rats. Conclusion: Exposure to TQ before conception potentiates focal seizure while suppresses generalized PTZ-induced seizure in rat offspring. TQ significantly changed the PTZ-induced seizure pattern in favor of focal seizure. 270 278 2019/05/112019/03/42019/01/62019/04/10 1398/1/21 2019/08/32019/07/232019/06/182019/07/7 1398/4/16 Amin Abdollahzade Fard Amin Abdollahzade Fard Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran Iran Ehsan Saboory Ehsan Saboory Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran Iran saboory@zums.ac.ir Yaghob Tahmazi Yaghob Tahmazi Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran Iran Yousef Rasmi Yousef Rasmi Department of Biochemistry, Faculty of Medicine, Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran Iran Thymoquinone Seizure Pentylenetetrazole Pre-gestation. Abdel-Rahman M, Arafa NM, El-khadragy MF, Kassab RB. 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The neuroprotective effects of thymoquinone: a review. Dose-response 2018; 16: 1559325818761455.##Guha D, Biswas D, Purkayastha S. Suppression of penicillin-induced epileptiform activity by nigella sativa: Possible mediation by neurotransmitters. Biogenic Amines 2005; 19: 309-322.##Heidari M, Dadollahi Z, Mehrabani M, Mehrabi H, Pourzadeh-Hosseini M, Behravan E, et al. Study of antiseizure effects of matricaria recutita extract in mice. Ann N Y Acad Sci 2009; 1171: 300-304.##Hosseinzadeh H, Khosravan V. Anticonvulsant effects of aqueous and ethanolic extracts of crocus sativus l stigmas in mice. Arch Iran Med 2002; 5: 44-47.##Hosseinzadeh H, Madanifard M. Anticonvulsant effects of coriandrum sativum l. Seed extracts in mice. Arch Iran Med 2000; 3: 81-84.##Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the major constituent of nigella sativa seeds, in mice. Phytomedicine 2004; 11: 56-64.##Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri M-T. Intracerebroventricular administration of thymoquinone, the major constituent of nigella sativa seeds, suppresses epileptic seizures in rats. Med Sci Monit 2005; 11: BR106-BR110.##Hunt PA, Hassold TJ. Human female meiosis: what makes a good egg go bad? Trends Genet 2008; 24: 86-93.##Ilhan A, Gurel A, Armutcu F, Kamisli S, Iraz M. Antiepileptogenic and antioxidant effects of nigella sativa oil against pentylenetetrazol-induced kindling in mice. Neuropharmacology 2005; 49: 456-464.##Kandratavicius L, Balista PA, Lopes-Aguiar C, Ruggiero RN, Umeoka EH, Garcia-Cairasco N, et al. Animal models of epilepsy: use and limitations. Neuropsychiatr Dis Treat 2014; 10: 1693-1705.##Krisher R. The effect of oocyte quality on development. J Anim Sci 2004; 82: E14-E23.##Mahmoodkhani M, Saboory E, Roshan-Milani S, Azizi N, Karimipour M, Rasmi Y, et al. Pregestational stress attenuated fertility rate in dams and increased seizure susceptibility in offspring. 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Motor defects, dopamine concentration and brain-derived neurotrophic factor in a rat model of Parkinson's disease can be affected by pre-infection with Toxoplasma gondii 2 2 Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder with progressive degeneration of dopaminergic neurons in the nigrostriatal system. Toxoplasma gondii (TG) is a parasite that has gene for tyrosine hydroxylase and can produce dopamine. It is not clear whether TG infection has an effect on PD and its motor defect or not. The aim of the present study was to investigate the effects of 6-hydroxydopamine (6-OHDA) model of PD on motor defects, striatal dopamine and brain-derived neurotrophic factor (BDNF) levels in pre-infected TG rats. Methods: Fifty Sprague-Dawley adult male rats weighing 200-300g were used in five groups. Induction of PD were done by unilateral intra-striatal injection of 6-OHDA, and to prove PD induction the animals were tested for drug-free elevated body swing behavior and bar test. Dopamine and BDNF concentration in striatum were measured by ELISA kits. Giemsa staining of brain smears confirmed TG infection. Results: The results showed that TG infection prior to PD induction attenuated the elevated body swing bias and the latency in movement on the bar compared to PD rats without infection. The levels of striatal dopamine and the BDNF in TG infected PD rats was significantly higher than the PD rats without infection. Conclusion: Motor defects in experimental 6-OHDA- induced PD rats can be improved by pre-infection with TG through the increased levels of striatal dopamine and BDNF. 279 285 2019/05/112019/03/42019/01/62019/04/102018/12/30 1397/10/9 2019/08/32019/07/232019/06/182019/07/72019/06/21 1398/3/31 Moslem Riyahi Moslem Riyahi Division of Physiology, Department of Basic Science, Shiraz University, Shiraz, Iran Iran Mahnaz Taherianfard Mahnaz Taherianfard Division of Physiology, Department of Basic Science, Shiraz University, Shiraz, Iran Iran taherian@shirazu.ac.ir Parkinson’s disease Toxoplasma gondii BDNF Dopamine. Beste C, Getzmann S, Gajewski PD, Golka K, Falkenstein M. Latent toxoplasma gondii infection leads to deficits in goal-directed behavior in healthy elderly. Neurobiology of aging 2014; 35: 1037-1044.##Beyer MMS. Long-term effects of immunostimulation on synaptic plasticity and neurodegeneration: Technische Universität Carolo-Wilhelmina zu Braunschweig, 2016.##Carter CJ. Toxoplasmosis and polygenic disease susceptibility genes: Extensive toxoplasma gondii host/pathogen interactome enrichment in nine psychiatric or neurological disorders. Journal of pathogens 2013; 2013.##Dickson DW. Parkinson’s disease and parkinsonism: Neuropathology. Cold Spring Harbor perspectives in medicine 2012; 2: a009258.##Garbayo E, Ansorena E, Blanco-Prieto MJ. Drug development in parkinson's disease: From emerging molecules to innovative drug delivery systems. Maturitas 2013; 76: 272-278.##Gaskell EA, Smith JE, Pinney JW, Westhead DR, McConkey GA. A unique dual activity amino acid hydroxylase in toxoplasma gondii. PloS one 2009; 4: e4801.##Gatkowska J, Wieczorek M, Dziadek B, Dzitko K, Dlugonska H. Sex-dependent neurotransmitter level changes in brains of toxoplasma gondii infected mice. Experimental parasitology 2013; 133: 1-7.##Miman O, Kusbeci OY, Aktepe OC, Cetinkaya Z. The probable relation between toxoplasma gondii and parkinson's disease. Neuroscience letters 2010; 475: 129-131.##Nayebi AM, Rad SR, Saberian M, Azimzadeh S, Samini M. Buspirone improves 6-hydroxydopamine-induced catalepsy through stimulation of nigral 5-ht1a receptors in rats. Pharmacological reports 2010; 62: 258-264.##Ödberg-Ferragut C, Renault JP, Viscogliosi E, Toursel C, Briche I, Engels A, et al. Molecular cloning, expression analysis and iron metal cofactor characterisation of a superoxide dismutase from toxoplasma gondii. Molecular and biochemical parasitology 2000; 106: 121-129.##Paxinos G, Watson C. The rat brain in stereotaxic coordinates. Germany: elsevier, 2004.##Prandovszky E, Gaskell E, Martin H, Dubey JP, Webster JP, McConkey GA. The neurotropic parasite toxoplasma gondii increases dopamine metabolism. PloS one 2011; 6: e23866.##Roghani M, Behzadi G, Baluchnejadmojarad T. Efficacy of elevated body swing test in the early model of parkinson's disease in rat. Physiology & behavior 2002; 76: 507-510.##Shulman JM, De Jager PL, Feany MB. 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Microrna-132 dysregulation in toxoplasma gondii infection has implications for dopamine signaling pathway. Neuroscience 2014; 268: 128-138.##Yurek DM, Fletcher-Turner A. Differential expression of gdnf, bdnf, and nt-3 in the aging nigrostriatal system following a neurotoxic lesion. Brain research 2001; 891: 228-235.## ##

Effects of carvacrol on spatial learning performances, hippocampal interleukin-1ß level and oxidative stress markers in lipopolysaccharide-treated rats 2 2 Introduction: Peripheral administration of lipopolysaccharide (LPS), can cause production of cytokines in the brain and subsequently impair learning and memory function. Carvacrol is a phenolic monoterpene that is found in the essential oils of the Lamiaceae family. Anti-inflammatory and antioxidant activities of carvacrol have been demonstrated in previous studies. The aim of the current study was to evaluate the effects of carvacrol on spatial learning performances in LPS-treated rats. Methods: Male Wistar rats were pretreated with carvacrol at doses of 10, 25 and 50mg/kg for a week. Then, the animals received LPS injection (1mg/kg, ip) and treatments continued for 3 more weeks. Spatial learning performances were assessed in rats by the Morris water maze from post-injection days 18 to 21. Biochemical assays (interleukine-1β, lipid peroxidation and total thiol levels) were performed in the hippocampus and cerebral cortex at the end of the experiment. Results: LPS-treated rats displayed higher escape latency and longer traveled distance as compared to control rats. In addition, chronic treatment of LPS-treated rats with carvacrol at a dose of 25mg/kg significantly decreased escape latency and traveled distance as compared to untreated-LPS rats. Biochemical assessments showed no significant difference in inflammatory and oxidative stress markers levels among the groups. Conclusion: Our findings demonstrated that chronic treatment with carvacrol improves spatial learning performances in LPS-treated rats. This might be due to antioxidant, anti-inflammatory and anticholinesterase activities of carvacrol in early LPS challenge. 286 295 2019/05/112019/03/42019/01/62019/04/102018/12/302019/04/24 1398/2/4 2019/08/32019/07/232019/06/182019/07/72019/06/212019/07/23 1398/5/1 Manizheh Gholami Manizheh Gholami Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Iran Ziba Rajaei Ziba Rajaei Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Iran rajaeiz@med.mui.ac.ir Maryam Malek Maryam Malek Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Iran Carvacrol Lipopolysaccharide Spatial learning Cytokines Oxidative stress Inflammation. Ahmad A, Khan A, Akhtar F, Yousuf S, Xess I, Khan LA, et al. Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida. 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Pterostilbene attenuates lipopolysaccharide-induced learning and memory impairment possibly via inhibiting microglia activation and protecting neuronal injury in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2014;54:92–102.##Houdek HM, Larson J, Watt JA, Rosenberger TA. Bacterial lipopolysaccharide induces a dose-dependent activation of neuroglia and loss of basal forebrain cholinergic cells in the rat brain. Inflamm Cell Signal. 2014;1:e47.##Joshi R, Garabadu D, Teja GR, Krishnamurthy S. Silibinin ameliorates LPS-induced memory deficits in experimental animals. Neurobiol Learn Mem. 2014;116:117-31.##Jukic M, Politeo O, Maksimovic M, Milos M, Milos M. In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytother Res. 2007;21:259-61.## ##Karkabounas S, Kostoula OK, Daskalou T, Veltsistas P, Karamousis M, Zelovitis I, et al. Anticarcinogenic and antiplatelet effects of carvacrol. 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Pelargonidin improves amyloid β-induced deficits in the long-term potentiation in hippocampus of male rats 2 2 Introduction: Given that pelargonidin is an anthocyanin that exhibits neuroprotective effects and Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid-beta (Aβ) and cognitive dysfunction subsequently, herein, we examined the effects of pelargonidin on Aβ-induced long-term potentiation deficits in rats. Methods: AD was induced using intrahippocampal injections of the Aβ in the adult Wistar male rats. The rats received single intraperitoneal injections of pelargonidin (3mg/kg). Long-term potentiation in the perforant path- dentate gyrus synapses was assessed electrophysiologically by measuring the field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude. Results: Our results showed that Aβ significantly decreased fEPSP slope and SP amplitude in comparison with the control and sham groups, whereas pelargonidin increased these parameters in comparison to the Aβ group. Conclusion: It is probably that pelargonidin could improve Aβ-induced cognition deficit in rats. 296 301 2019/05/112019/03/42019/01/62019/04/102018/12/302019/04/242019/03/16 1397/12/25 2019/08/32019/07/232019/06/182019/07/72019/06/212019/07/232019/08/3 1398/5/12 Sara Soleimani Asl Sara Soleimani Asl Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Iran Marek J. Łos Marek J. Łos Małopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland Poland Mehdi Mehdizadeh Mehdi Mehdizadeh Cellular and Molecular Research Center, Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran Iran mehdizadeh.m@iums.ac.ir Amyloid β-peptide Pelargonidin Long- term potentiation Hippocampus. 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The role of muscarinic and serotonergic-2A receptors in the antinociceptive effect of pregabalin 2 2 Introduction: Pregabalin (PGB) is an analog of gamma-aminobutyric acid (GABA) with antinociceptive, antihyperalgesic and antiallodynic properties which frequently used in clinical pain management. Effect of PBG in neuropathic pain, incisional-inflammatory injury, post-operational pain, chronic pain and experimental pain models have already shown. It has been already known that muscarinic and serotonergic-2A receptors have a role in pain transmission. Methods: in this study, role of muscarinic and serotonergic-2A receptors in antinociceptive effect of pregabalin were evaluated with hot-plate and tail flick tests and effects of administered drugs on locomotor activity were measured with automated activity cage. Results: PGB treatment (30 and 100mg/kg) caused longer latency in hot plate and tail flick tests than saline group. That antinociceptive effect of pregabalin abolished by ketanserin (1mg/kg) and atropine (1mg/kg) treatment. Conclusion: However, there is lack of knowledge about role of nociceptive pathways underlying pregabalin mediated antinociception. Our results suggest that cholinergic and serotonergic systems have a role in antinociceptive effect of PGB which has seen in these somatic pain tests. 302 308 2019/05/112019/03/42019/01/62019/04/102018/12/302019/04/242019/03/162019/03/19 1397/12/28 2019/08/32019/07/232019/06/182019/07/72019/06/212019/07/232019/08/32019/07/23 1398/5/1 Mohamad Hallak Mohamad Hallak Erciyes University, School of Medicine, Deparment of Pharmacology 38039 Melikgazi, Kayserı, Turkey Turkey Hakan Balci Hakan Balci Ondokuz Mayıs University, School of Medicine, Deparment of Pharmacology 55139, Atakum, Samsun, Turkey Turkey Caner Günaydın Caner Günaydın Ondokuz Mayıs University, School of Medicine, Deparment of Pharmacology 55139, Atakum, Samsun, Turkey Turkey S. Sirri Bilge S. Sirri Bilge Ondokuz Mayıs University, School of Medicine, Deparment of Pharmacology 55139, Atakum, Samsun, Turkey Turkey ssbilge@omu.edu.tr Pregabalin Somatic pain Ketanserin Atropine. Avery MC, Krichmar JL. Neuromodulatory systems and their interactions: a review of models, theories, and experiments. Front Neural Circuits 2017; 11: 108.##Bardin L. The complex role of serotonin and 5-HT receptors in chronic pain. Behav Pharmacol 2011; 22: 390-404.##Bartolini A, Di Cesare Mannelli L, Ghelardini C. Analgesic and antineuropathic drugs acting through central cholinergic mechanisms. Recent Pat CNS Drug Discov 2011; 6: p. 119-40.##Chen SR, Pan HL. Activation of muscarinic receptors inhibits spinal dorsal horn projection neurons: role of GABAB receptors. Neuroscience 2004; 125: 141-8.##Dolphin AC. The α2δ subunits of voltage-gated calcium channels. Biochim Biophys Acta 2013; 1828: 1541-9.##Fehrenbacher JC, Taylor CP, Vasko MR. Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain 2003; 105: 133-41.##Foroud M, Vesal N. Evaluation of the anti-nociceptive effects of morphine, tramadol, meloxicam and their combinations using the tail-flick test in rats. Vet Res Forum 2015; 6: 313-8.##Gore M, Sadosky A, Tai KS, Stacey B. A retrospective evaluation of the use of gabapentin and pregabalin in patients with postherpetic neuralgia in usual-care settings. Clin Ther 2007; 29: 1655-70.##Hayashida KI, Bynum T, Vincler M, Eisenach JC. Inhibitory M2 muscarinic receptors are upregulated in both axotomized and intact small diameter dorsal root ganglion cells after peripheral nerve injury. Neuroscience 2006; 140: 259-68.##Honda K, Murao N, Ibuki T, Kamiya HO, Takano Y. The role of spinal muscarinic acetylcholine receptors in clonidine-induced anti-nociceptive effects in rats. Biol Pharm Bull 2003; 26: 1178-80.##Kaygisiz B, Kilic FS, Senguleroglu N, Baydemir C, Erol K. The antinociceptive effect and mechanisms of action of pregabalin in mice. Pharmacol Rep 2015; 67: 129-33.##Kommalage M, Höglund AU. Involvement of spinal serotonin receptors in the regulation of intraspinal acetylcholine release. Eur J Pharmacol 2005; 509: 127-34.##Kurihara T, Nonaka T, Tanabe T. Acetic acid conditioning stimulus induces long-lasting antinociception of somatic inflammatory pain. Pharmacol Biochem Behav 2003; 74: 841-9.##Luszczki JJ. Dose-response relationship analysis of pregabalin doses and their antinociceptive effects in hot-plate test in mice. Pharmacol Rep 2010; 62: 942-8.##Marks DM, Patkar AA, Masand PS, Pae CU. Does pregabalin have neuropsychotropic effects?: a short perspective. Psychiatry Investig 2009; 6: 55-8.##Martino G, Puma C, Yu XH, Gilbert AK, Coupal M, Markoglou N, et al. The M1/M4 preferring agonist xanomeline is analgesic in rodent models of chronic inflammatory and neuropathic pain via central site of action. Pain 2011; 152: 2852-60.##Meymandi MS, Keyhanfar F, Yazdanpanah O, Heravi G. The role of NMDARs ligands on antinociceptive effects of pregabalin in the tail flick test. Anesth Pain Med 2015; 5: e28968.##Pinardi G, Sierralta F, Miranda HF. Atropine reverses the antinociception of nonsteroidal anti-inflammatory drugs in the tail-flick test of mice. Pharmacol Biochem Behav 2003; 74: 603-8.##Rashid MH, Ueda H. Neuropathy-specific analgesic action of intrathecal nicotinic agonists and its spinal GABA-mediated mechanism. Brain Res 2002; 953: 53-62.##Rashvand M, Khajavai A, Parviz M, Hasanein P, Keshavarz M. GABAA receptors are involved in the analgesic effects of morphine microinjected into the central nucleus of the amygdala. Clin Exp Pharmacol Physiol 2014; 41: 338-44.##Ravnefjord A, Brusberg M, Larsson H, Lindström E, Martínez V. Effects of pregabalin on visceral pain responses and colonic compliance in rats. Br J Pharmacol 2008; 155: 407-16.##Ripamonti CI. Pain management. Ann Oncol 2012; 10: x294-301.##Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nat Med 2004; 10: 685-92.##Ruggieri V, Vitale G, Pini LA, Sandrini M. Differential involvement of opioidergic and serotonergic systems in the antinociceptive activity of N-arachidonoyl-phenolamine (AM404) in the rat: comparison with paracetamol. Naunyn Schmiedebergs Arch Pharmacol 2008; 377: 219-29.##Sandrini M, Vitale G, Pini LA. Central antinociceptive activity of acetylsalicylic acid is modulated by brain serotonin receptor subtypes. Pharmacology 2002; 65: 193-7.##Santos AR, Gadotti VM, Oliveira GL, Tibola D, Paszcuk AF, Neto A, et al. Mechanisms involved in the antinociception caused by agmatine in mice. Neuropharmacology 2005; 48: 1021-34.##Shamsi Meymandi M, Keyhanfar F. Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain. Can J Anaesth 2013; 60: 44-9. ##Sikandar S, Dickenson AH. Pregabalin modulation of spinal and brainstem visceral nociceptive processing. Pain 2011; 152: 2312-22.##Xie DJ, Uta D, Feng PY, Wakita M, Shin MC, Furue H, et al. Identification of 5-HT receptor subtypes enhancing inhibitory transmission in the rat spinal dorsal horn in vitro. Mol Pain 2012; 8: 58.## ##

Gender differences in nitric oxide and antioxidant response to physical stress in tissues of trained mice after hyperbaric oxygen preconditioning 2 2 Introduction: The aim of this study was to evaluate gender differences in the oxidant/antioxidant response in different tissues of trained mice during physical stress with the hyperbaric oxygen preconditioning (HBOP) beforehand. Methods: Trained mice of both genders treated by HBOP were divided into three groups including basal, fasting and prolonged exercise. Parameters of oxidant/antioxidant state including nitric oxide (NO) were measured in blood and tissues. Gender differences in the effects of HBOP were analyzed in the basal levels, fasting and in the net response to exercise. Results: HBOP diminished the elevated basal levels of lipoperoxidation, NO, antioxidant enzymes and glutathione in liver of females only, compared to untreated group. A similar decrease in the basal levels of NO and enzymes was observed in other tissues of females as well. A strong decrease of basal level of glutathione in liver coincided to its increase in muscle, brain, small intestine and adipose tissue. Therefore, females after HBOP started prolonged exercise with a lower basal level of oxidative stress and antioxidant defense in liver but increased basal levels of glutathione in most tissues. Consequently, during exercise, females showed a strong net response in the liver and stability in muscle tissue, while in males the contrary response was found. Conclusion: Only in the tissues of females did HBOP drastically affect the basal levels of the oxidant/antioxidant status. Although performance decreased in both genders, it was better in females, likely related to the redistribution of glutathione from the liver to other tissues after HBOP. 309 321 2019/05/112019/03/42019/01/62019/04/102018/12/302019/04/242019/03/162019/03/192018/12/10 1397/9/19 2019/08/32019/07/232019/06/182019/07/72019/06/212019/07/232019/08/32019/07/232019/07/1 1398/4/10 Alexandre Kormanovski Alexandre Kormanovski Instituto Politécnico Nacional, Escuela Superior de Medicina, Sección de Estudios de Posgrado e Investigación, Mexico City, Mexico Mexico Maria del Carmen Castillo-Hernández Maria del Carmen Castillo-Hernández Instituto Politécnico Nacional, Escuela Superior de Medicina, Sección de Estudios de Posgrado e Investigación, Mexico City, Mexico Mexico ccastillohe@ipn.mx Gustavo Guevara-Balcázar Gustavo Guevara-Balcázar Instituto Politécnico Nacional, Escuela Superior de Medicina, Sección de Estudios de Posgrado e Investigación, Mexico City, Mexico Mexico Teresa Pérez Teresa Pérez Instituto Politécnico Nacional, Escuela Superior de Medicina, Sección de Estudios de Posgrado e Investigación, Mexico City, Mexico Mexico Eleazar Lara-Padilla Eleazar Lara-Padilla Instituto Politécnico Nacional, Escuela Superior de Medicina, Sección de Estudios de Posgrado e Investigación, Mexico City, Mexico Mexico Gender difference Oxidative stress Antioxidant Nitric oxide Hyperbaric oxygen. 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Nitric oxide regulation of microvascular oxygen. Antioxid Redox Signal 2007; 9: 829-43. ##Buras JA, Stahl GL, Svoboda KK, Reenstra WR. Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. Am J Physiol Cell Physiol 2000; 278: C292-302.##Cabigas BP, Su J, Hutchins W, Shi Y, Schaefer RB, Recinos RF, et al. Hyperoxic and hyperbaric-induced cardioprotection: role of nitric oxide synthase 3. Cardiovasc Res 2006; 72: 143-51.##Castillo-Hernandez MC, Lara-Padilla E, Kormanovski A, Perez-Tuñon JG, Lopez-Calderon EM, Guevara-Balcazar G. Normalization of QRS segment, blood pressure and heartbeat in an experimental model of amintriptyline intoxication in rats following hyperbaric oxygenation therapy. Int J Pharmac 2015; 11: 508-12.##Cheng O, Ostrowski RP, Wu B, Liu W, Chen C, Zhang JH. Cyclooxygenase-2 mediates hyperbaric oxygen preconditioning in the rat model of transient global cerebral ischemia. 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The impact of serum bilirubin on diabetic nephropathy and pulmonary function in type II diabetic patients 2 2 Introduction: Diabetes mellitus may be associated with many complications including diabetic nephropathy and pulmonary impairment, the pathogenesis and progression of these complications may be related to oxidative stress. Bilirubin, which is a non-polar molecule have antioxidant properties. The relationship between occurrence, development and prognosis of diabetic complications and bilirubin concentration had become a research focus. However, no study has evaluated the relationship between protective effect of bilirubin on both diabetic nephropathy and pulmonary impairment in type II diabetic patients. Methods: The design of the study is a cross sectional study included 245 type II diabetic patients. Spirometry was done for all patients. Albumin/creatinine ratio (ACR), glycosylated hemoglobin, total serum bilirubin and serum glutathione reductase enzyme were measured. Results: There was a significant statistical negative relationship between serum bilirubin and glutathione reductase enzyme with ACR and significant statistical positive relationship between serum bilirubin and glutathione reductase enzyme with lung function parameters (forced expiratory volume in the first second and forced vital capacity). Conclusion: serum bilirubin levels had a protective effect against diabetic nephropathy and impairment of pulmonary function. If serum bilirubin levels were moderately high but within the normal range, this was related with decreased risk of diabetic complications and there was a parallel relationship between serum bilirubin levels and the glutathione reductase enzyme levels in type II diabetic patients. 322 329 2019/05/112019/03/42019/01/62019/04/102018/12/302019/04/242019/03/162019/03/192018/12/102018/10/1 1397/7/9 2019/08/32019/07/232019/06/182019/07/72019/06/212019/07/232019/08/32019/07/232019/07/12019/07/23 1398/5/1 Nibras H. Abdulsada Al-Ghuraibawi Nibras H. Abdulsada Al-Ghuraibawi Department of Pharmacology, College of Pharmacy, University of Kufa, Kufa, Iraq Iraq nibrash.abdalsada@uokufa.edu.iq Zahraa Al-Mudhafer Zahraa Al-Mudhafer Department of Physiology, College of Medicine, University of Kufa, Iraq Iraq Salam J. Mohammed Salam J. Mohammed Department of Community Medicine, College of Medicine, University of Kufa, Kufa, Iraq Iraq Bilirubin Diabetes mellitus type II Diabetic nephropathy Pulmonary impairment Oxidative stress. Ali MO. Pulmonary complications in diabetes mellitus. Mymensingh Med J 2014; 23: 603-5.##American diabetes association. Executive summary: standards of medical care in diabetes-2012. Diabetes Care 2012; 35: S4-S10.##Apperley S, Park HY, Holmes DT, Man SP, Tashkin D, Wise RA, et al. Serum bilirubin and disease progression in mild COPD. Chest 2015; 148: 169-175.##Arora V, Kulkarni RK, Cherian S, Pillai R, Shivali M. Hyperbilirubinemia in normal healthy donors. Asian J Transfus Sci 2009; 3: 70-72.##Beckman JA, Creager MA. Vascular complications of diabetes. Circ Res 2016; 118: 1771-85.##Charles Patrick Davis, Bhupinder S Anand. Bilirubin and bilirubin blood test. MedicineNet 2018.##Curjuric I, Imboden M, Adam M, Bettschart RW, Gerbase MW, Künzli N, et al. Serum bilirubin is associated with lung function in a Swiss general population sample. Eur Respir J 2014; 43: 1278-88.##da Silva Almeida R, de Melo RC, Chaves MS, Baptista GM, Margotto SS, de Oliveira Andrade LJ. Diabetic pneumopathy. Braz J Med Biol Res 2016; 4: 21-28.##Fukui M, Tanaka M, Shiraishi E, Harusato I, Hosoda H, Asano M, et al. Relationship between serum bilirubin and albuminuria in patients with type 2 diabetes. Kidney Int 2008; 74: 1197-201.##Gazzin S, Vitek L, Watchko J, Shapiro SM, Tiribelli C. A novel perspective on the biology of bilirubin in health and disease. Trends Mol Med 2016; 22: 758-68.##Gläser S, Krüger S, Merkel M, Bramlage P, Herth FJ. 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Corrigendum to “Insulin attenuates 6-OHDA induced cell death in human neuroblastoma cells and restores p-Akt/t-Akt level” [Physiol Pharmacol 23 (2019) 115-122] 2 2 Introduction: Human neuroblastoma cell line is used in studying Parkinson’s disease (PD) due to its similarities to dopaminergic neurons. 6-hydroxydopamine (6-OHDA), a catecholaminergic neurotoxin, has been widely used to induce cell death in cellular models of PD. Although the brain glucose entry is not dependent on insulin, this peptide has been reported to have a role in PD, in which insulin signaling disruption is reported. This study aimed to evaluate, if insulin is efficient in preventing 6-OHDA induced cell death in human neuroblastoma cells as well as its effect on phoshorylated Akt (p-Akt)/total Akt (t-Akt) ratio. Methods: The cells -grown in DMEM/F12 media supplemented with 10% fetal bovine serum- were exposed to 6-OHDA with/without insulin for 24h, and then MTT assay was done to examine their viability. A pilot study was performed to assess the protective doses of insulin and accordingly the doses 0.9 and 1mM were selected. Western blot assay was done to evaluate the effect of 6-OHDA or insulin on p-Akt and t-Akt level. Results: The results indicated that insulin has potency to prevent SH-SY5Y cell death, and p-Akt/t-Akt decline induced by 6-OHDA. Conclusion: The results suggested insulin as a protective agent in dopaminergic cells. 330 330 2019/05/112019/03/42019/01/62019/04/102018/12/302019/04/242019/03/162019/03/192018/12/102018/10/12020/01/7 1398/10/17 2019/08/32019/07/232019/06/182019/07/72019/06/212019/07/232019/08/32019/07/232019/07/12019/07/232020/01/7 1398/10/17 رکسانا Soukhaklari Roxana Soukhaklari Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Iran Rasoul Ghasemi Rasoul Ghasemi Neurophysiology Research Center and Department of Physiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Maryam Moosavi Maryam Moosavi Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Iran marmoosavi@sums.ac.ir Insulin Parkinson’s disease 6-OHDA SH-SY5Y Akt. Amiri E, Ghasemi R, Moosavi M. Agmatine protects against 6-ohda-induced apoptosis, and erk and akt/gsk disruption in sh-sy5y cells. 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