2020年12月
Low-Level Inhibition of GABAergic Synapses Enhances Gene Expressions Crucial for Neuronal Plasticity in the Hippocampus After Ischemic Stroke
Journal of Stroke and Cerebrovascular Diseases
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- 巻
- 29
- 号
- 12
- 開始ページ
- 105316
- 終了ページ
- 105316
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.jstrokecerebrovasdis.2020.105316
- 出版者・発行元
- Elsevier BV
OBJECTIVE: Pharmacological inhibition of GABAergic synapses could represent a potent neuromodulation strategy to activate hippocampal neurons and increase neurotrophic factor gene expression, thus exerting a beneficial effect on post-stroke cognitive impairment (PSCI). The objective of this study was to assess the effects of low-level inhibition of GABAergic synapses on hippocampal gene expressions related to neuroplasticity using the middle cerebral artery occlusion surgery (MCAO) ischemic stroke rat model. METHODS: The animals were randomly assigned to three experimental groups-(1) a sham operated group (SHAM), (2) a control group (CON), and (3) a bicuculline group (BIC). MCAO was performed in the CON and BIC groups. A non-epileptic dose of bicuculline (0.25 mg/kg) was intraperitoneally administered every day for two weeks, starting three days after surgery, to the rats in the BIC group. The mRNA expression of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), in relation to neurotrophic intracellular signal, p75, in relation to apoptosis, and synaptophysin (SYP) and PSD-95, synaptic markers, were assessed in the hippocampus ipsilateral to the ischemic site. RESULTS: MCAO increased the gene expression of TrkB. Furthermore, MCAO plus bicuculline administration increased the expression ratio of TrkB to p75 and SYP gene expression. CONCLUSION: Therefore, this study showed that administration of bicuculline after stroke beneficially modulated the expression of crucial genes for neuroplasticity, including BDNF receptors and SYP, in the ipsilateral hippocampus, suggesting that low-level inhibition of GABAergic synapses could lead to beneficial neuromodulation in the hippocampus after stroke.
- リンク情報
- ID情報
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- DOI : 10.1016/j.jstrokecerebrovasdis.2020.105316
- ISSN : 1052-3057
- PubMed ID : 32992173