Postischemic Anhedonia Associated with Neurodegenerative Changes in the Hippocampal Dentate Gyrus of Rats.
Postischemic Anhedonia Associated with Neurodegenerative Changes in the Hippocampal Dentate Gyrus of Rats.
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DOI：
10.1155/2016/5054275
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发表时间：
2016
影响因子：
3.1
通讯作者：
Oka N
中科院分区：
文献类型：
--
作者：
Kasahara J;Uchida H;Tezuka K;Oka N
脑卒中后抑郁是脑卒中慢性期（如脑缺血）的主要症状之一。然而，其病理生理机制还不清楚。使用短暂的右侧大脑中动脉闭塞（MCAO-，90分钟）作为本研究的缺血模型，我们首先观察到，加重的快感缺失自发发生，特别是在20周后的MCAO，它是防止慢性抗抑郁药治疗（丙咪嗪或氟伏沙明）。快感缺失与海马齿状回同侧颗粒神经元的丢失有关，抗抑郁药丙咪嗪也能预防这种快感缺失。免疫组化分析显示，颗粒细胞层内的细胞凋亡增加之前，并与神经元的损失，丙咪嗪似乎恢复生存信号，而不是抑制死亡信号，以防止神经元凋亡。MCAO后1周内，同侧和对侧海马颗粒下区神经干细胞的增殖和发育均短暂增加，6周后逐渐减少，几乎停止，而丙咪嗪治疗可部分阻止其增殖和发育。总的来说，我们的研究提出了新的见解，脑卒中后抑郁症和海马齿状回的迟发性神经退行性变化与有效使用抗抑郁药之间的机制相关性。
Poststroke depression is one of the major symptoms observed in the chronic stage of brain stroke such as cerebral ischemia. Its pathophysiological mechanisms, however, are not well understood. Using the transient right middle cerebral artery occlusion- (MCAO-, 90 min) operated rats as an ischemia model in this study, we first observed that aggravation of anhedonia spontaneously occurred especially after 20 weeks of MCAO, and it was prevented by chronic antidepressants treatment (imipramine or fluvoxamine). The anhedonia specifically associated with loss of the granular neurons in the ipsilateral side of hippocampal dentate gyrus and was also prevented by an antidepressant imipramine. Immunohistochemical analysis showed increased apoptosis inside the granular cell layer prior to and associated with the neuronal loss, and imipramine seemed to recover the survival signal rather than suppressing the death signal to prevent neurons from apoptosis. Proliferation and development of the neural stem cells were increased transiently in the subgranular zone of both ipsi- and contralateral hippocampus within one week after MCAO and then decreased and almost ceased after 6 weeks of MCAO, while chronic imipramine treatment prevented them partially. Overall, our study suggests new insights for the mechanistic correlation between poststroke depression and the delayed neurodegenerative changes in the hippocampal dentate gyrus with effective use of antidepressants on them.