Priming of microglia in a DNA-repair deficient model of accelerated aging

• DOI: 10.1016/j.neurobiolaging.2014.03.025
• Publication Date: 2014-03-28T17:35:15Z
• Authors: Divya D.A. Raj; Dick Jaarsma; Inge R. Holtman; Marta Olah; Filipa M. Ferreira; Wandert Schaafsma; Nieske Brouwer; Michel M. Meijer; Monique C. de Waard; Ingrid van der Pl...; Renata Brandt; Karim L. Kreft; Jon D. Laman; Gerald de Haan; Knut P.H. Biber; Jan H.J. Hoeijmakers; Bart J.L. Eggen; Hendrikus W.G.M. ...
• Keywords: Priming (agriculture); ERCC1; Senescence

Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to age-related deterioration CNS. The most prominent change enhanced sensitivity inflammatory stimuli, referred as priming. It unclear if priming due intrinsic ageing or induced by neural environment. We have studied this Ercc1 mutant mice, a DNA repair-deficient mouse model displays features accelerated aging multiple tissues including In showed hallmark such an exaggerated response peripheral lipopolysaccharide exposure terms cytokine expression phagocytosis. Specific targeting deletion forebrain neurons resulted progressive exemplified phenotypic alterations. Summarizing, these data show neuronal genotoxic stress sufficient switch from resting primed state.