Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
J Neurochem. 2019 May;149(4):488-498. doi: 10.1111/jnc.14691. Epub 2019 Apr 2.
Electroconvulsive seizure (ECS), a model of electroconvulsive therapy in rodents, strongly increases neurogenesis in the adult hippocampus. Neurogenesis is a multi-step process that spans proliferation, survival, neuronal differentiation, and functional maturation. Our previous study demonstrated that ECS stimulates the proliferation of neural stem-like cells. However, the contribution of ECS to survival, neuronal differentiation, and maturation in newborn cells remains unknown. To evaluate the effect of ECS on these processes, we labeled newborn cells with bromodeoxyuridine (BrdU) before ECS treatment to determine the cell age and examined the survival rate and expression of cellular markers in the BrdU-labeled cells. Our results revealed that exposure to ECS (11 repetitions) during the differentiation phase significantly increased survival and promoted neuronal differentiation of newborn cells in the dentate gyrus. Four of ECS repetitions during the early differentiation phase were sufficient to promote dendritic outgrowth in immature neurons and enhance the expression of the immature neuronal marker, calretinin, in newborn cells. In contrast, exposure to ECS (11 repetitions) during the late maturation phase significantly suppressed the expression of the mature neuronal marker, calbindin, in newborn neurons. These results demonstrate that ECS during the differentiation phase promoted survival and neuronal differentiation and, in contrast, suppressed mature marker expression during the late maturation phase, suggesting that ECS has multiple effects on the different stages of adult neurogenesis.
电惊厥发作(ECS),一种啮齿动物电惊厥疗法的模型,强烈增加成年海马体中的神经发生。神经发生是一个多步骤的过程,包括增殖、存活、神经元分化和功能成熟。我们之前的研究表明,ECS 刺激神经干细胞样细胞的增殖。然而,ECS 对新生细胞存活、神经元分化和成熟的贡献尚不清楚。为了评估 ECS 对这些过程的影响,我们在 ECS 治疗前用溴脱氧尿苷(BrdU)标记新生细胞,以确定细胞年龄,并检查 BrdU 标记细胞的存活率和细胞标志物的表达。我们的结果表明,在分化阶段暴露于 ECS(11 次重复)显著增加了新生细胞在齿状回中的存活并促进了其神经元分化。在早期分化阶段进行 4 次 ECS 重复足以促进未成熟神经元的树突生长,并增强新生细胞中未成熟神经元标志物 calretinin 的表达。相比之下,在成熟后期暴露于 ECS(11 次重复)显著抑制了新生神经元中成熟神经元标志物 calbindin 的表达。这些结果表明,在分化阶段的 ECS 促进了存活和神经元分化,而在成熟后期则抑制了成熟标志物的表达,表明 ECS 对成年神经发生的不同阶段有多种影响。