Changes in the Density of Nitrergic Neurons in the Hippocampus of Rats Following Kainic Acid and Melatonin Administration
Changes in the Density of Nitrergic Neurons in the Hippocampus of Rats Following Kainic Acid and Melatonin Administration
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DOI：
10.33549/physiolres.932295
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发表时间：
2013-01-01
影响因子：
2.1
通讯作者：
Bhatnagar, M.
中科院分区：
文献类型：
--
作者：
Jain, A.;Sharma, D.;Bhatnagar, M.
一氧化氮（NO）可能在兴奋性毒性的病理生理学中发挥作用。这也是可能的，增加Ca 2+超载和NO介导的事件参与兴奋性毒性过程中的神经元损失。采用尼克酰胺腺嘌呤二核苷酸磷酸-黄递酶（NADPH-d）组织化学方法，观察了褪黑素对海人酸（KA）兴奋性中毒后大鼠海马NADPH-d阳性神经元的影响。还研究了所有相应实验组中的细胞溶质Ca 2+（游离钙）。以10 mg/kg/bw（体重）的单次剂量给予动物红藻氨酸。KA处理的大鼠以20 mg/kg/bw的剂量给予褪黑激素（持续14天）。在处理的最后一天，在深度硫喷妥钠麻醉下，用4%多聚甲醛经心脏灌注动物。切下冷冻切片（20 μ m）并对NADPH-d阳性神经元染色。KA暴露组海马齿状回（DG）背侧叶、腹侧叶、海马门区、CA 1和CA 3区NADPH-d阳性神经元数量显著增加，胞内游离Ca ~（2+）浓度也相应增加。KA +褪黑激素处理组DG、门区、CA 1和CA 3区NADPH-d阳性神经元数量减少，胞浆Ca ~（2+）浓度降低。我们的研究表明，细胞内Ca ~（2+）和一氧化氮（NO）水平的升高在红藻氨酸诱导的兴奋性毒性中起重要作用。抑制NO的产生可能是褪黑素减轻氧化损伤的另一途径，在神经保护中起重要作用。
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 mu m) 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.