小胶质细胞
神经发生
神经营养因子
神经科学
海马结构
神经可塑性
双皮质醇
海马体
脑源性神经营养因子
神经干细胞
齿状回
生物
细胞生物学
神经营养素
心理学
祖细胞
室下区
神经母细胞
医学
炎症
免疫学
干细胞
内科学
受体
作者
Samuel Harley,Emily F. Willis,Samreen Shaikh,Daniel G. Blackmore,Pankaj Sah,Marc J. Ruitenberg,Perry F. Bartlett,Jana Vukovic
标识
DOI:10.1523/jneurosci.2539-20.2021
摘要
Microglia, the resident immune cells of the CNS, have emerged as key regulators of neural precursor cell activity in the adult brain. However, the microglia-derived factors that mediate these effects remain largely unknown. In the present study, we investigated a role for microglial brain-derived neurotrophic factor (BDNF), a neurotrophic factor with well known effects on neuronal survival and plasticity. Surprisingly, we found that selective genetic ablation of BDNF from microglia increased the production of newborn neurons under both physiological and inflammatory conditions (e.g., LPS-induced infection and traumatic brain injury). Genetic ablation of BDNF from microglia otherwise also interfered with self-renewal/proliferation, reducing their overall density. In conclusion, we identify microglial BDNF as an important factor regulating microglia population dynamics and states, which in turn influences neurogenesis under both homeostatic and pathologic conditions.SIGNIFICANCE STATEMENT (1) Microglial BDNF contributes to self-renewal and density of microglia in the brain. (2) Selective ablation of BDNF in microglia stimulates neural precursor proliferation. (3) Loss of microglial BDNF augments working memory following traumatic brain injury. (4) Benefits of repopulating microglia on brain injury are not mediated via microglial BDNF.
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