TY - JOUR
T1 - Priming of microglia in a DNA-repair deficient model of accelerated aging
AU - Raj, Divya D. A.
AU - Jaarsma, Dick
AU - Holtman, Inge R.
AU - Olah, Marta
AU - Ferreira, Filipa M.
AU - Schaafsma, Wandert
AU - Brouwer, Nieske
AU - Meijer, Michel M.
AU - de Waard, Monique C.
AU - van der Pluijm, Ingrid
AU - Brandt, Renata
AU - Kreft, Karim L.
AU - Laman, Jon D.
AU - de Haan, Gerald
AU - Biber, Knut P. H.
AU - Hoeijmakers, Jan H. J.
AU - Eggen, Bart J. L.
AU - Boddeke, Hendrikus W. G. M.
PY - 2014
Y1 - 2014
N2 - 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. © 2014 Elsevier Inc.
AB - 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. © 2014 Elsevier Inc.
UR - https://www.scopus.com/pages/publications/84902072810
UR - https://www.ncbi.nlm.nih.gov/pubmed/24799273
U2 - 10.1016/j.neurobiolaging.2014.03.025
DO - 10.1016/j.neurobiolaging.2014.03.025
M3 - Article
C2 - 24799273
SN - 0197-4580
VL - 35
SP - 2147
EP - 2160
JO - Neurobiology of aging
JF - Neurobiology of aging
IS - 9
ER -