Laboratory of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, Tokyo 158-8501, Japan, and Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
J Neurosci. 2014 Feb 5;34(6):2231-43. doi: 10.1523/JNEUROSCI.1619-13.2014.
Although microglia have long been considered as brain resident immune cells, increasing evidence suggests that they also have physiological roles in the development of the normal CNS. In this study, we found large numbers of activated microglia in the forebrain subventricular zone (SVZ) of the rat from P1 to P10. Pharmacological suppression of the activation, which produces a decrease in levels of a number of proinflammatory cytokines (i.e., IL-1β, IL-6, TNF-α, and IFN-γ) significantly inhibited neurogenesis and oligodendrogenesis in the SVZ. In vitro neurosphere assays reproduced the enhancement of neurogenesis and oligodendrogenesis by activated microglia and showed that the cytokines revealed the effects complementarily. These results suggest that activated microglia accumulate in the early postnatal SVZ and that they enhance neurogenesis and oligodendrogenesis via released cytokines.
尽管小胶质细胞长期以来被认为是大脑驻留的免疫细胞，但越来越多的证据表明，它们在正常中枢神经系统的发育中也具有生理作用。在这项研究中，我们发现从 P1 到 P10 大鼠的前脑室下区 (SVZ) 中有大量激活的小胶质细胞。药物抑制其激活，会导致许多促炎细胞因子（即 IL-1β、IL-6、TNF-α 和 IFN-γ）水平下降，从而显著抑制 SVZ 中的神经发生和少突胶质细胞发生。体外神经球测定再现了激活的小胶质细胞对神经发生和少突胶质细胞发生的增强作用，并表明细胞因子具有互补的作用。这些结果表明，激活的小胶质细胞在出生后早期 SVZ 中积累，并且它们通过释放的细胞因子增强神经发生和少突胶质细胞发生。
