title: Repression of telomere-associated genes by microglia activation in neuropsychiatric disease.
abstract: Microglia senescence may promote neuropsychiatric disease. This prompted us to examine the relationship between microglia activation states and telomere biology. A panel of candidate genes associated with telomere maintenance, mitochondrial biogenesis, and cell-cycle regulation were investigated in M1- and M2-polarized microglia in vitro as well as in MACS-purified CD11b+ microglia/brain macrophages from models of stroke, Alzheimer's disease, and chronic stress. M1 polarization, ischemia, and Alzheimer pathology elicited a strikingly similar transcriptomic profile with, in particular, reduced expression of murine Tert. Our results link classical microglia activation with repression of telomere-associated genes, suggesting a new mechanism underlying microglia dysfunction.
authors.affiliation: Klinik für Psychiatrie und Psychotherapie, Charité Campus Mitte, Berlin, Germany.|Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany.|Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin, Berlin, Germany.|Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsmedizin Rostock, Gehlsheimer Straße 20, 18147, Rostock, Germany.
authors.forename: Golo
authors.initials: G
authors.lastname: Kronenberg
authors.affiliation: Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany.|Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Ria
authors.initials: R
authors.lastname: Uhlemann
authors.affiliation: Klinik für Psychiatrie und Psychotherapie, Charité Campus Mitte, Berlin, Germany.|Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany.|Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schöner
authors.affiliation: Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany.|Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wegner
authors.affiliation: Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany.|Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Valérie
authors.initials: V
authors.lastname: Boujon
authors.affiliation: Institut für Neuropathologie, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Deigendesch
authors.affiliation: Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany.|Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin, Berlin, Germany.|German Center for Neurodegenerative Diseases (DZNE), Charitéplatz 1, 10117, Berlin, Germany.|Cluster of Excellence NeuroCure, Charité - Universitätsmedizin, Berlin, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Endres
authors.affiliation: Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany. karen.gertz@charite.de.|Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin, Berlin, Germany. karen.gertz@charite.de.
authors.forename: Karen
authors.initials: K
authors.lastname: Gertz
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016207:Cytokines; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D053764:Presenilin-1; D012333:RNA, Messenger; D019098:Telomerase; C509187:Tert protein, mouse
keywords: Alzheimer’s disease; Microglia; Mitochondrial biogenesis; Neurodegenerative disease; Telomerase