Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, Mannheim, Germany; Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, Mannheim, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Germany.
Hippocampus. 2013 Dec;23(12):1321-30. doi: 10.1002/hipo.22171. Epub 2013 Sep 2.
Electroconvulsive therapy (ECT) is a uniquely effective treatment for major depressive disorder. An increase in hippocampal neurogenesis is implicated in the recovery from depression. We used an inducible genetic mouse model in which only GFAP-expressing stem-like cells (type-1 cells) and their progeny are selectively labeled with the reporter protein β-galactosidase to track the process of neurogenesis in the dentate gyrus over 3 months following electroconvulsive seizures (ECS), the mouse equivalent of ECT. All ECS protocols tested induced a transient increase in type-1 cell divisions. While this led to an expansion of the type-1 cell pool after high-frequency ECS sessions for 5 consecutive days (5-ECS), asymmetric divisions drove neurogenesis by giving rise to Doublecortin (DCX)-expressing neuroblasts that matured into NeuN+ neurons. Significantly, the increase in newly generated DCX+ and NeuN+ cells after 5-ECS could be traced back to proliferating type-1 cells. Low-frequency continuation ECS (c-ECS) consisting of five single ECS sessions administered every 2 weeks resulted in a similar increase in newborn neurons as the high-frequency 5-ECS protocol. Moreover, the combination of 5-ECS and c-ECS led to a further significant increase in newborn neurons, suggesting a cellular mechanism responsible for the propitious effects of high-frequency ECT followed by continuation ECT in severely depressed patients. The ability of high- and low-frequency ECS to induce normally quiescent type-1 cells to proliferate and generate new neurons sets it apart from other antidepressant treatments and may underlie the superior clinical efficacy of ECT.
电抽搐治疗（ECT）是治疗重度抑郁症的一种独特有效方法。海马神经发生的增加与抑郁的恢复有关。我们使用了一种可诱导的基因小鼠模型，其中只有 GFAP 表达的干细胞（1 型细胞）及其后代被β-半乳糖苷酶报告蛋白选择性标记，以追踪电抽搐后 3 个月内齿状回的神经发生过程（ECT 的小鼠等效物）。所有测试的 ECT 方案都诱导了 1 型细胞分裂的短暂增加。虽然这导致高频 ECS 连续 5 天（5-ECT）后 1 型细胞池扩大，但不对称分裂通过产生表达 Doublecortin（DCX）的神经前体细胞，使其成熟为 NeuN+神经元，从而驱动神经发生。重要的是，5-ECT 后新产生的 DCX+和 NeuN+细胞的增加可以追溯到增殖的 1 型细胞。由 5 个单次 ECS 组成的低频延续 ECS（c-ECT），每 2 周给药一次，导致新生神经元的增加与高频 5-ECT 方案相似。此外，5-ECT 和 c-ECT 的组合导致新生神经元进一步显著增加，表明高频 ECT 后继续 ECT 对严重抑郁患者有益的细胞机制。高、低频 ECT 诱导通常静止的 1 型细胞增殖并产生新神经元的能力使其有别于其他抗抑郁治疗方法，可能是 ECT 临床疗效优异的基础。
