Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6

被引:450
作者
Vallières, L
Campbell, IL
Gage, FH
Sawchenko, PE
机构
[1] Salk Inst Biol Studies, Neuronal Struct & Funct Lab, La Jolla, CA 92037 USA
[2] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA
关键词
postnatal neurogenesis; neural progenitor cells; interleukin-6; proinflammatory cytokine; chronic inflammation; hippocampus; transgenic mice; Fluoro-jade;
D O I
10.1523/JNEUROSCI.22-02-00486.2002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Postnatal neurogenesis can be modulated after brain injury, but the role of the attendant expression of inflammatory mediators in such responses remains to be determined. Here we report that transgenically directed production of interleukin-6 (IL-6) by astroglia decreased overall neurogenesis by 63% in the hippocampal dentate gyrus of young adult transgenic mice. The proliferation, survival, and differentiation of neural progenitor cells labeled with the thymidine analog bromodeoxyuridine were all reduced in the granule cell layer of these mice, whereas their distribution and gliogenesis appeared normal. These effects were not a consequence of general toxicity of the IL-6 transgene, because they were manifested in the absence of neuronal death and of major changes in glial cell number and morphology. These findings suggest that long-term exposure of the brain to proinflammatory mediators such as IL-6, as is seen in certain degenerative disorders and infections, can interfere with adult neurogenesis.
引用
收藏
页码:486 / 492
页数:7
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