title: Changes in the density of nitrergic neurons in the hippocampus of rats following kainic acid and melatonin administration.
abstract: Nitric oxide (NO) may play a role in the pathophysiology of excitotoxicity. It is also possible that increase in Ca²⁺ overload and NO-mediated events are involved in neuronal loss during excitotoxicity. Using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry, we have investigated the effects of melatonin on NADPH-d positive hippocampal neurons after kainic acid (KA) induced excitotoxicity in female rats of Wistar strain. Cytosolic Ca²⁺ (free calcium) in all the respective experimental groups was also studied. Kainic acid was administered, with a single dose of 10 mg/kg/bw (body weight) to the animals. KA treated rats were given melatonin at a dose of 20 mg/kg/bw (for 14 day). On the last day of treatment, animals were transcardially perfused with 4 % paraformaldehyde under deep thiopental anaesthesia. Cryostat sections (20 microm) were cut and stained for NADPH-d positive neurons. KA exposed animals showed a significantly increased number of NADPH-d positive neurons in the dorsal and ventral blade of the dentate gyrus (DG), hilus, CA1 and CA3 area of hippocampus, with a parallel increase in intracellular free Ca²⁺ ion concentration, as compared to the control group. KA + melatonin-treated animal groups showed reduced number of NADPH-d positive neurons in DG, hilus, CA1 and CA3 areas and a decline in cytosolic Ca²⁺ concentration, as compared to KA treated group. Our study suggests that the enhanced levels of cytosolic Ca²⁺ and nitric oxide (NO) play an important role in kainate induced excitotoxicity. Inhibition of NO production may be another means whereby melatonin can reduce oxidative damage and seems to play important role in neuroprotection.
authors.affiliation: Department of Zoology, University College of Science, M. L. Sukhadia University, Udaipur, India.
authors.forename: A
authors.initials: A
authors.lastname: Jain
authors.forename: D
authors.initials: D
authors.lastname: Sharma
authors.forename: P
authors.initials: P
authors.lastname: Suhalka
authors.forename: P
authors.initials: P
authors.lastname: Sukhwal
authors.forename: M
authors.initials: M
authors.lastname: Bhatnagar
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018690:Excitatory Amino Acid Agonists; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; D008550:Melatonin; D007608:Kainic Acid; D002118:Calcium