Serial electroconvulsive Seizure alters dendritic complexity and promotes cellular proliferation in the mouse dentate gyrus; a role for Egr3.

Serial electroconvulsive Seizure alters dendritic complexity and promotes cellular proliferation in the mouse dentate gyrus; a role for Egr3.
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DOI:
10.1016/j.brs.2023.04.022
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发表时间:
2023-05
期刊:
影响因子:
7.7
通讯作者:
Gallitano, A. L.
Gallitano, A. L.
中科院分区:
医学1区
文献类型:
--
作者:
Meyers, K. T.;Damphousse, C. C.;Ozols, A. B.;Campbell, J. M.;Newbern, J. M.;Hu, C.;Marrone, D. F.;Gallitano, A. L.

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尽管电休克疗法是治疗严重心境障碍最安全、最有效的方法之一,但其治疗机制仍不清楚。电惊厥发作(ECS)诱导快速,高水平的立即早期基因(IEGs)和脑源性神经营养因子(BDNF)的表达,除了刺激神经发生和树突重塑的齿状回(DG)神经元。我们先前已经表明,这种BDNF的上调未能发生在缺乏IEG Egr 3的小鼠海马中。由于BDNF影响神经发生和树突重塑,我们假设Egr 3 −/−小鼠将表现出神经发生和树突重塑的缺陷,以响应ECS。为了验证这一假设,我们研究了重复ECS后Egr 3 −/−和野生型小鼠DG中的树突重塑和细胞增殖。小鼠每天接受10次ECS。在Golgi-Cox染色的组织中检查树突状形态,并通过溴脱氧尿苷(BrdU)免疫组织化学和共聚焦成像分析细胞增殖。小鼠中的连续ECS导致DG中的树突状重塑、棘密度增加和细胞增殖。Egr 3的丢失改变了由连续ECS诱导的树突状重塑,但不改变树突棘的数量或ECS的细胞增殖结果。Egr 3影响ECS诱导的树突状细胞重塑,但不是ECS诱导的海马DG细胞增殖所必需的。
Despite being one of the safest, most effective treatments for severe mood disorders, the therapeutic mechanisms of electroconvulsive therapy remain unknown. Electroconvulsive seizure (ECS) induces rapid, high-level expression of immediate early genes (IEGs) and brain-derived neurotrophic factor (BDNF), in addition to stimulation of neurogenesis and dendritic remodeling of dentate gyrus (DG) neurons. We have previously shown that this upregulation of BDNF fails to occur in the hippocampus of mice lacking the IEG Egr3. Since BDNF influences neurogenesis and dendritic remodeling, we hypothesized that Egr3−/− mice will exhibit deficits in neurogenesis and dendritic remodeling in response to ECS. To test this hypothesis, we examined dendritic remodeling and cellular proliferation in the DG of Egr3−/− and wild-type mice following repeated ECS. Mice received 10 daily ECSs. Dendritic morphology was examined in Golgi-Cox-stained tissue and cellular proliferation was analyzed through bromodeoxyuridine (BrdU) immunohistochemistry and confocal imaging. Serial ECS in mice results in dendritic remodeling, increased spine density, and cellular proliferation in the DG. Loss of Egr3 alters the dendritic remodeling induced by serial ECS but does not change the number of dendritic spines or cellular proliferation consequences of ECS. Egr3 influences the dendritic remodeling induced by ECS but is not required for ECS-induced proliferation of hippocampal DG cells.
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