Expression of ALS-linked TDP-43 mutant in astrocytes causes non-cell-autonomous motor neuron death in rats.

ABSTRACT: Mutation of Tar DNA-binding protein 43 (TDP-43) is linked to amyotrophic lateral sclerosis. Although astrocytes have important roles in neuron function and survival, their potential contribution to TDP-43 pathogenesis is unclear. Here, we created novel lines of transgenic rats that express a mutant form of human TDP-43 (M337V substitution) restricted to astrocytes. Selective expression of mutant TDP-43 in astrocytes caused a progressive loss of motor neurons and the denervation atrophy of skeletal muscles, resulting in progressive paralysis. The spinal cord of transgenic rats also exhibited a progressive depletion of the astroglial glutamate transporters GLT-1 and GLAST. Astrocytic expression of mutant TDP-43 led to activation of astrocytes and microglia, with an induction of the neurotoxi

SUBMITTER: Tong J 

PROVIDER: S-EPMC3981181 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature