title: Telomere dysfunction reduces microglial numbers without fully inducing an aging phenotype.
abstract: The susceptibility of the aging brain to neurodegenerative disease may in part be attributed to cellular aging of the microglial cells that survey it. We investigated the effect of cellular aging induced by telomere shortening on microglia by the use of mice lacking the telomerase RNA component (TERC) and design-based stereology. TERC knockout (KO) mice had a significantly reduced number of CD11b(+) microglia in the dentate gyrus. Because of an even greater reduction in dentate gyrus volume, microglial density was, however, increased. Microglia in TERC KO mice maintained a homogenous distribution and normal expression of CD45 and CD68 and the aging marker, ferritin, but were morphologically distinct from microglia in both adult and old wild-type mice. TERC KO mice also showed increased cellular apoptosis and impaired spatial learning. Our results suggest that individual microglia are relatively resistant to telomerase deficiency during steady state conditions, despite an overall reduction in microglial numbers. Furthermore, telomerase deficiency and aging may provide disparate cues leading to distinct changes in microglial morphology and phenotype.
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
authors.forename: Asif Manzoor
authors.initials: AM
authors.lastname: Khan
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: Babcock
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.
authors.forename: Hamid
authors.initials: H
authors.lastname: Saeed
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
authors.forename: Christa Løth
authors.initials: CL
authors.lastname: Myhre
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark. Electronic address: bfinsen@health.sdu.dk.
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017209:Apoptosis / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000473:pathology; D005293:Ferritins; D017493:Leukocyte Common Antigens; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology*; D019636:Neurodegenerative Diseases; D010641:Phenotype; D012313:RNA / Q000235:genetics*; D065853:Spatial Learning; D019098:Telomerase / Q000172:deficiency* / Q000235:genetics*; D016615:Telomere / Q000473:pathology* / Q000502:physiology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005293:Ferritins; D017493:Leukocyte Common Antigens; D012313:RNA; D019098:Telomerase; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C422952:telomerase RNA; C516770:Ptprc protein, mouse
keywords: Cellular apoptosis; Dentate gyrus; Global spatial sampling; Optical fractionator; Replicative senescence; Spatial learning