Matsuda Taito, Nakashima Kinichi
Department of Stem Cell Biology and Medicine; Graduate School of Medical Sciences; Kyushu University ; Fukuoka, Japan.
Neurogenesis (Austin). 2015 Nov 25;2(1):e1081714. doi: 10.1080/23262133.2015.1081714. eCollection 2015.
A population of proliferating neural stem/progenitor cells located in the subgranular zone of the adult hippocampal dentate gyrus (DG) gives rise to new neurons continuously throughout life, and this process is referred to as adult hippocampal neurogenesis. To date, it has generally been accepted that impairments of adult hippocampal neurogenesis resulting from pathological conditions such as stress, ischemia and epilepsy lead to deficits in hippocampus-dependent learning and memory tasks. Recently, we have discovered that microglia, the major immune cells in the brain, attenuate seizure-induced aberrant hippocampal neurogenesis to withstand cognitive decline and recurrent seizure. In that study, we further showed that Toll-like receptor 9, known as a pathogen-sensing receptor for innate immune system activation, recognizes self-DNA derived from degenerating neurons to induce TNF-α production in the microglia after seizure, resulting in inhibition of seizure-induced aberrant neurogenesis. Our findings provide new evidence that interaction between the innate immune and nervous systems ensures homeostatic neurogenesis in the adult hippocampus and should pave the way for the development of new therapeutic strategies for neurological diseases including epilepsy.
位于成年海马齿状回（DG）颗粒下区的一群增殖性神经干细胞/祖细胞在一生中持续产生新的神经元，这一过程被称为成年海马神经发生。迄今为止，人们普遍认为，由压力、缺血和癫痫等病理状况导致的成年海马神经发生受损会导致依赖海马的学习和记忆任务出现缺陷。最近，我们发现，作为大脑主要免疫细胞的小胶质细胞可减轻癫痫诱导的异常海马神经发生，以抵御认知衰退和癫痫复发。在该研究中，我们进一步表明，作为一种用于激活先天性免疫系统的病原体传感受体，Toll样受体9可识别源自退化神经元的自身DNA，从而在癫痫发作后诱导小胶质细胞产生肿瘤坏死因子-α（TNF-α），进而抑制癫痫诱导的异常神经发生。我们的研究结果提供了新的证据，即先天性免疫系统和神经系统之间的相互作用可确保成年海马的稳态神经发生，并应为包括癫痫在内的神经疾病新治疗策略的开发铺平道路。
