GABA(B) receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice.
GABA(B) receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice.
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GABA(B) 受体拮抗剂可促进小鼠急性脑缺血后海马神经发生并促进认知功能恢复。
DOI：
10.1186/s13287-020-02059-x
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发表时间：
2021-01-07
影响因子：
7.5
通讯作者：
Cheng O
中科院分区：
文献类型：
--
作者：
Song D;Chen Y;Chen C;Chen L;Cheng O
已有研究表明，促进内源性神经发生对脑缺血（CI）所致认知功能障碍的恢复具有重要意义。药物抑制GABAB受体可促进成年健康小鼠和抑郁小鼠的神经发生。在这项研究中，我们打算研究GABAB受体拮抗剂对脑缺血后小鼠认知功能和海马神经发生的影响。成年小鼠双侧颈总动脉闭塞（BCCAO） 20 min诱导CI， CI后24 h开始用CGP52432 （GABAB受体拮抗剂，CGP， 10 mg/kg腹腔注射）治疗。第28天采用Morris水迷宫测试大鼠空间学习记忆能力。第14、28天采用免疫荧光法检测DG区神经发生。体外实验采用CCK8和免疫荧光法检测细胞增殖，ELISA法和Western blot法检测cAMP/CREB信号通路相关蛋白的表达。CGP可显著改善脑缺血所致的空间学习记忆障碍，增强神经干细胞（NSCs）的增殖、未成熟神经元数量和新生细胞向神经元的分化。体外实验进一步证实CGP剂量依赖性地增强了NSCs的细胞活力，免疫荧光染色显示CGP促进了NSCs的增殖。此外，CGP治疗增加了培养的NSCs中cAMP、PKA和pCREB的表达。抑制GABAB受体可有效促进脑缺血后成年小鼠海马神经发生，改善空间学习记忆。
Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.
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DOI：
10.1016/j.bbi.2016.01.017
发表时间：
2016-11
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Chesnokova V;Pechnick RN;Wawrowsky K
通讯作者：
Wawrowsky K
影响因子：
4.6
作者：
He, Wei-Ming;Ying-Fu, Li;Peng, Yu-Ping
通讯作者：
Peng, Yu-Ping
影响因子：
5
作者：
LANZA, M;FASSIO, A;RAITERI, M
通讯作者：
RAITERI, M
影响因子：
8.3
作者：
Komitova, M;Mattsson, B;Eriksson, PS
通讯作者：
Eriksson, PS
影响因子：
3.4
作者：
Couillard-Despres, S;Winner, B;Aigner, L
通讯作者：
Aigner, L