Loss of TGF-β1 leads to increased neuronal cell death and microgliosis in mouse brain

被引:302
作者
Brionne, TC
Tesseur, I
Masliah, E
Wyss-Coray, T [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA
[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
[4] GRECC, VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA
关键词
D O I
10.1016/S0896-6273(03)00766-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
TGF-beta1 is a key regulator of diverse biological processes in many tissues and cell types, but its exact function in the developing and adult mammalian CNS is still unknown. We report that lack of TGF-beta1 expression in neonatal Tgfb1(-/-) mice results in a widespread increase in degenerating neurons accompanied by reduced expression of synaptophysin and laminin and a prominent microgliosis. Lack of TGF-beta1 also strongly reduces survival of primary neurons cultured from Tgfb1(-/-) mice. TGF-beta1 deficiency in adult Tgfb1(-/+) mice results in increased neuronal susceptibility to excitotoxic injury, whereas astroglial overexpression of TGF-beta1 protects adult mice against neurodegeneration in acute, excitotoxic and chronic injury paradigms. This study reveals a nonredundant function for TGF-beta1 in maintaining neuronal integrity and survival of CNS neurons and in regulating microglial activation. Because individual TGF-beta1 expression levels in the brain vary considerably between humans, this finding could have important implications for susceptibility to neurodegeneration.
引用
收藏
页码:1133 / 1145
页数:13
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