Loss of TGF-[beta]1 Leads to Increased Neuronal Cell Death and Microgliosis in Mouse Brain

TGF-β1 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-β1 expression in neonatalTgfb1-/-mice results in a widespread increase in degenerating neurons accom...

Full description

Saved in:
Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2003-12, Vol.40 (6), p.1133
Main Authors: Brionne, Thomas C, Tesseur, Ina, Masliah, Eliezer, Wyss-Coray, Tony
Format: Article
Language:English
Subjects:
Apoptosis
Brain
Cell death
Gene expression
Genotype & phenotype
Insects
Kinases
Mammals
Phosphorylation
Proteins
Rodents
Software
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:TGF-β1 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-β1 expression in neonatalTgfb1-/-mice results in a widespread increase in degenerating neurons accompanied by reduced expression of synaptophysin and laminin and a prominent microgliosis. Lack of TGF-β1 also strongly reduces survival of primary neurons cultured fromTgfb1-/-mice. TGF-β1 deficiency in adultTgfb1-/+mice results in increased neuronal susceptibility to excitotoxic injury, whereas astroglial overexpression of TGF-β1 protects adult mice against neurodegeneration in acute, excitotoxic and chronic injury paradigms. This study reveals a nonredundant function for TGF-β1 in maintaining neuronal integrity and survival of CNS neurons and in regulating microglial activation. Because individual TGF-β1 expression levels in the brain vary considerably between humans, this finding could have important implications for susceptibility to neurodegeneration.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(03)00766-9