TY - JOUR
T1 - Telomere dysfunction reduces microglial numbers without fully inducing an aging phenotype
AU - Khan, Asif Manzoor
AU - Babcock, Alicia A
AU - Saeed, Hamid
AU - Myhre, Christa Løth
AU - Kassem, Moustapha
AU - Finsen, Bente
N1 - Copyright © 2015 Elsevier Inc. All rights reserved.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.neurobiolaging.2015.03.008
DO - 10.1016/j.neurobiolaging.2015.03.008
M3 - Journal article
C2 - 25892207
SN - 0197-4580
VL - 36
SP - 2164
EP - 2175
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 6
ER -