Ekdahl Christine T, Claasen Jan-Hendrik, Bonde Sara, Kokaia Zaal, Lindvall Olle
Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, Biomedical Center A-11, Lund, Sweden.
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13632-7. doi: 10.1073/pnas.2234031100. Epub 2003 Oct 27.
New hippocampal neurons are continuously generated in the adult brain. Here, we demonstrate that lipopolysaccharide-induced inflammation, which gives rise to microglia activation in the area where the new neurons are born, strongly impairs basal hippocampal neurogenesis in rats. The increased neurogenesis triggered by a brain insult is also attenuated if it is associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. The impaired neurogenesis in inflammation is restored by systemic administration of minocycline, which inhibits microglia activation. Our data raise the possibility that suppression of hippocampal neurogenesis by activated microglia contributes to cognitive dysfunction in aging, dementia, epilepsy, and other conditions leading to brain inflammation.
成年大脑中会持续生成新的海马神经元。在此,我们证明脂多糖诱导的炎症会导致新生神经元所在区域的小胶质细胞活化,这会严重损害大鼠海马的基础神经发生。如果脑损伤引发的神经发生增加与组织损伤或脂多糖注入引起的小胶质细胞活化相关,那么这种增加也会减弱。通过全身给予米诺环素抑制小胶质细胞活化,可恢复炎症中受损的神经发生。我们的数据提出了一种可能性,即活化的小胶质细胞对海马神经发生的抑制作用可能导致衰老、痴呆、癫痫以及其他导致脑部炎症的疾病中的认知功能障碍。