حیدرنیا کلاتی, زینب (2018) بررسی نقش گیرنده¬های سروتونینی 5-HT1A بر روند نوروژنز ناحیه¬ی شکنج دندانه¬دار درتشنج¬های ناشی از کیندلینگ الکتریکی موش صحرایی. Masters thesis, علوم پزشکی سبزوار.
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Abstract
Introduction: Due to the high prevalence of temporal lobe epilepsy and Lack of definite treatment for it, Understanding the mechanisms involved in the onset, expansion, and inhibition of seizure is necessary. In previous studies, have indicated that dentate gyrus has a high density of 5-HT1A serotonin receptors, which is one of the effective factors in the inhibition of seizures. On the other hand, the activator-5-HT1A serotonin receptors play an important role in the proliferation of neurogenic prognostic or neurogenesis. Therefore, the purpose of this study was to investigate the role of 5-HT1A receptors on the neurogenesis of dentate gyrus in seizures of the electrical kindling model. Materials and Methods: 36 male rats (280 ± 30 gr) were divided into six groups: (1) Sham, (2)kindle, (3)kindle+vehicle, (4)kindle+5-HT1A receptor Antagonist (WAY100635,5µg,IV) (5) Kindle + neurogenesis inhibitor (7-nitroindazole, 7-NI; 15mg/kg), (6)kindle+ WAY100635 + 7-NI were randomly assigned to each group (n=6). The field potentials of dentate gyrus were recorded daily for 20 minutes. Animals in the control group became completely kindled before 10 days , So the stimuli were applied to all groups within 10 days (12 times a day with a 5 minute interval). WAY100635 was injected 30 min before application of the kindling stimulus into the right lateral ventricle of the animals. The 7-NI drug was injected intra ventricle 20 minutes before kindling. In all groups, within 10 days, the seizure quantities and electrophysiologic quantities recorded and measured. Finally, the expression level of GFAP in the sub-granular zone dentate gyrus, as an indicator of neurogenesis in this area, was measured by immunohistochemistry. Results: Data analysis showed that the Way100635 and 7-NI Way100635 groups were significantly faster than the control group (P<0.001). Repeated measures two-way ANOVA and Bonferroni indicated that changes in After-discharge duration in the Way100635 group increased by 10 days in comparison with the control group and decreased in the 7-NI -Way100635 group compared to the control group, but not significant (P> 0.05) and also the slope of fEPSP at the end of 10 days in the 7-NI -Way100635 group was significantly decreased than the control group (p<0.001). Immunohistochemistry showed that cell proliferation significantly increased in the 7-NI Way100635 group compared to the control group (p <0.001). Conclusion: In summary, the increase in seizure behaviors following injection of 5-HT1A receptor antagonists indicates the anticonvulsant effects of these receptors on seizures caused by perforant pathway electrical kindling. According to the reduced effects of 7NI on severity of seizures and synaptic potentiation, it can be concluded that inhibition of neuronogenesis in the dentate gyrus (by Inhibitionof nNOS), by enhancing the release of inhibitory neurotransmitters, Increases the Inhibitory activity of the hippocampal circuits and prevents the spread of seizures.. In addition, since injection of 7NI and WAY100635 together resulted in moderating seizure behaviors, decreasing synaptic potentiation and increasing cell proliferation compared to the Kindle+vehicle group, Therefore, it is conceivable that the 5-HT1A receptor and neuronal nitric oxide synthase in Inhibition neurogenesis and preventing the spread of seizures.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | تشنج، سرتونین، کیندلینگ، نوروژنز |
| Subjects: | Q Science > QP Physiology |
| Divisions: | Faculty of Medicine, Health and Life Sciences > School of Medicine |
| Depositing User: | Saeed Shoja |
| Date Deposited: | 24 Dec 2018 06:24 |
| Last Modified: | 24 Dec 2018 06:24 |
| URI: | http://eprints.medsab.ac.ir/id/eprint/770 |
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