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

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 Pluijm, 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. Boddeke*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

73 Citaten (Scopus)
53 Downloads (Pure)


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 the age-related deterioration of the CNS. The most prominent age-related change of microglia is enhanced sensitivity to inflammatory stimuli, referred to as priming. It is unclear if priming is due to intrinsic microglia ageing or induced by the ageing neural environment. We have studied this in Ercc1 mutant mice, a DNA repair-deficient mouse model that displays features of accelerated aging in multiple tissues including the CNS. In Ercc1 mutant mice, microglia showed hallmark features of priming such as an exaggerated response to peripheral lipopolysaccharide exposure in terms of cytokine expression and phagocytosis. Specific targeting of the Ercc1 deletion to forebrain neurons resulted in a progressive priming response in microglia exemplified by phenotypic alterations. Summarizing, these data show that neuronal genotoxic stress is sufficient to switch microglia from a resting to a primed state. (C) 2014 Elsevier Inc. All rights reserved.

Originele taal-2English
Pagina's (van-tot)2147-2160
Aantal pagina's14
TijdschriftNeurobiology of Aging
Nummer van het tijdschrift9
StatusPublished - sep-2014

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