Ifngr1 and Stat1 mediated canonical Ifn-γ signaling drives nigrostriatal degeneration.

ABSTRACT: Brain expression of AAV-Ifn-γ leads to reactive gliosis, nigrostriatal degeneration and midbrain calcification in wild type mice. This mouse model phenocopies idiopathic basal ganglia calcification which is associated with Parkinsonian symptoms. To understand how the nigro-striatal pathway is selectively vulnerable to Ifn-γ, we determined if the phenotype is driven by canonical signaling intermediates, Ifngr1 and Stat1. Using focused bioinformatic analysis and rotarod testing, we show that neuroinflammation and motor abnormalities precede the appearance of midbrain neuropathologies in the brains of Ifn-γ mouse model. To test whether canonical Ifn-γ signaling is a key driver of progressive nigrostriatal degeneration, we overexpressed Ifn-γ in the brains of Ifngr1^-/- and Stat1

SUBMITTER: Strickland MR 

PROVIDER: S-EPMC5748010 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature