Epigenetic enhancement of brain-derived neurotrophic factor signaling pathway improves cognitive impairments induced by isoflurane exposure in aged rats.
Epigenetic enhancement of brain-derived neurotrophic factor signaling pathway improves cognitive impairments induced by isoflurane exposure in aged rats.
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脑源性神经营养因子信号通路的表观遗传增强可改善老年大鼠因异氟烷暴露引起的认知障碍。
DOI：
10.1007/s12035-014-8659-z
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发表时间：
2014-12
影响因子：
5.1
通讯作者：
Yang, JianJun
中科院分区：
文献类型：
--
作者：
Ji, MuHuo;Dong, Lin;Jia, Min;Liu, WenXue;Zhang, MingQiang;Ju, LinSha;Yang, JiaoJiao;Xie, Zhongcong;Yang, JianJun
异氟醚诱导的认知障碍在动物模型中已有很好的记录;然而，分子机制在很大程度上仍有待确定。在本研究中，22月龄雄性Sprague-Dawley大鼠连续3天每天接受2小时1.5%异氟烷或100%氧气。对于干预研究，在异氟烷暴露前2 h，向大鼠腹腔内注射1.2 g/kg丁酸钠。我们的数据显示，重复异氟烷暴露显著减少了恐惧条件反射测试中的背景冻结时间和音调冻结时间，这与组蛋白去乙酰化酶2的上调，组蛋白乙酰化的减少以及海马中炎症和凋亡的增加有关，以及脑源性神经营养因子（BDNF）-酪氨酸激酶受体B（Trk B）和下游信号通路磷酸钙调蛋白-依赖性蛋白激酶和磷酸化cAMP反应元件结合蛋白。这些结果表明，异氟烷诱导的认知障碍与染色质组蛋白乙酰化的下降以及由此导致的BDNF-TrkB信号通路的下调有关。此外，组蛋白去乙酰化酶抑制剂丁酸钠可以挽救认知障碍和信号转导缺陷。因此，表观遗传增强BDNF-TrkB信号转导可能是逆转异氟烷诱导的认知障碍的有希望的策略。
Isoflurane-induced cognitive impairments are well documented in animal models; yet, the molecular mechanisms remain largely to be determined. In the present study, 22-month-old male Sprague-Dawley rats received 2 h of 1.5 % isoflurane or 100 % oxygen daily for 3 consecutive days. For the intervention study, the rats were intraperitoneally injected with 1.2 g/kg sodium butyrate 2 h before isoflurane exposure. Our data showed that repeated isoflurane exposure significantly decreased the freezing time to context and the freezing time to tone in the fear conditioning test, which was associated with upregulated histone deacetylase 2, reduced histone acetylation, and increased inflammation and apoptosis in the hippocampus, and impairments of brain-derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB) and the downstream signaling pathway phospho-calmodulin-dependent protein kinase and phospho-cAMP response element-binding protein. These results suggest that isoflurane-induced cognitive impairments are associated with the declines in chromatin histone acetylation and the resulting downregulation of BDNF-TrkB signaling pathway. Moreover, the cognitive impairments and the signaling deficits can be rescued by histone deacetylase inhibitor sodium butyrate. Therefore, epigenetic enhancement of BDNF-TrkB signaling may be a promising strategy for reversing isoflurane-induced cognitive impairments.
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影响因子：
120.7
作者：
WILLIAMSRUSSO, P;SHARROCK, NE;CHARLSON, ME
通讯作者：
CHARLSON, ME
影响因子：
6.1
作者：
Hsieh J;Eisch AJ
通讯作者：
Eisch AJ
白介素-1β在术后认知功能障碍中的作用。
影响因子：
11.2
作者：
Cibelli M;Fidalgo AR;Terrando N;Ma D;Monaco C;Feldmann M;Takata M;Lever IJ;Nanchahal J;Fanselow MS;Maze M
通讯作者：
Maze M
影响因子：
8.8
作者：
Steinmetz, Jacob;Christensen, Karl Bang;Rasmussen, Lars S.
通讯作者：
Rasmussen, Lars S.
影响因子：
7.6
作者：
Diogenes, Maria J.;Costenla, Ana R.;Sebastiao, Ana M.
通讯作者：
Sebastiao, Ana M.