Telomere dysfunction reduces microglial numbers without fully inducing an aging phenotype.

Asif Manzoor Khan, Alicia Babcock, Hamid Saeed, Christa Løth Myhre, Moustapha Kassem, Bente Finsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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.
OriginalsprogEngelsk
TidsskriftNeurobiology of Aging
Vol/bind36
Udgave nummer6
Sider (fra-til)2164-2175
Antal sider12
ISSN0197-4580
DOI
StatusUdgivet - jun. 2015

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