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Age related changes in microglial phenotype vary between CNS regions: grey versus white matter differences

Age related changes in microglial phenotype vary between CNS regions: grey versus white matter differences
Age related changes in microglial phenotype vary between CNS regions: grey versus white matter differences
Subtle regional differences in microglial phenotype exist in the adult mouse brain. We investigated whether these differences were amplified during ageing and following systemic challenge with lipopolysaccharide (LPS). We studied microglial morphology and phenotype in young (4mo) and aged (21mo) C57/BL6 mice using immunohistochemistry and quantified the expression levels of surface molecules on microglia in white and grey matter along the rostral-caudal neuraxis. We detected significant regional, age dependent differences in microglial phenotypes, with the microglia of white matter and caudal areas of the CNS exhibiting greater upregulation of CD11b, CD68, CD11c, F4/80 and Fc?RI than grey matter and rostral CNS areas. Upregulation of CD11c with age was restricted to the white matter, as was the appearance of multinucleated giant cells. Systemic LPS caused a subtle upregulation of Fc?RI after 24h, but the other markers examined were not affected. Burrowing behaviour and static rod assays were used to assess hippocampal and cerebellar integrity. Aged mice exhibited exaggerated and prolonged burrowing deficits following systemic LPS injection, while in the absence of an inflammatory challenge aged mice performed significantly worse than young mice in the static rod test. Taken together, these findings show that the effects of age on microglial phenotype and functional integrity vary significantly between CNS compartments, as do, albeit to a lesser extent, the effects of systemic LPS.
ageing, microglia, regional differences, behaviour, lps, CD11c, white matter
0889-1591
754-765
Hart, Adam D.
e5aa7d8f-47a2-408a-a9c9-fce7df90bdca
Wyttenbach, Andreas
71036eb1-f86e-4076-b079-308b1d1e4f91
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Hart, Adam D.
e5aa7d8f-47a2-408a-a9c9-fce7df90bdca
Wyttenbach, Andreas
71036eb1-f86e-4076-b079-308b1d1e4f91
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a

Hart, Adam D., Wyttenbach, Andreas and Perry, V. Hugh et al. (2012) Age related changes in microglial phenotype vary between CNS regions: grey versus white matter differences. [in special issue: Aging, Brain, Behavior and Immunity] Brain, Behavior and Immunity, 26 (5), 754-765. (doi:10.1016/j.bbi.2011.11.006). (PMID:22155499)

Record type: Article

Abstract

Subtle regional differences in microglial phenotype exist in the adult mouse brain. We investigated whether these differences were amplified during ageing and following systemic challenge with lipopolysaccharide (LPS). We studied microglial morphology and phenotype in young (4mo) and aged (21mo) C57/BL6 mice using immunohistochemistry and quantified the expression levels of surface molecules on microglia in white and grey matter along the rostral-caudal neuraxis. We detected significant regional, age dependent differences in microglial phenotypes, with the microglia of white matter and caudal areas of the CNS exhibiting greater upregulation of CD11b, CD68, CD11c, F4/80 and Fc?RI than grey matter and rostral CNS areas. Upregulation of CD11c with age was restricted to the white matter, as was the appearance of multinucleated giant cells. Systemic LPS caused a subtle upregulation of Fc?RI after 24h, but the other markers examined were not affected. Burrowing behaviour and static rod assays were used to assess hippocampal and cerebellar integrity. Aged mice exhibited exaggerated and prolonged burrowing deficits following systemic LPS injection, while in the absence of an inflammatory challenge aged mice performed significantly worse than young mice in the static rod test. Taken together, these findings show that the effects of age on microglial phenotype and functional integrity vary significantly between CNS compartments, as do, albeit to a lesser extent, the effects of systemic LPS.

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Accepted/In Press date: 2 December 2011
e-pub ahead of print date: May 2012
Published date: July 2012
Keywords: ageing, microglia, regional differences, behaviour, lps, CD11c, white matter
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 339979
URI: http://eprints.soton.ac.uk/id/eprint/339979
ISSN: 0889-1591
PURE UUID: 88b13e28-d81f-4477-8bbd-2ab723ae4268
ORCID for Jessica L. Teeling: ORCID iD orcid.org/0000-0003-4004-7391

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Date deposited: 06 Jun 2012 13:16
Last modified: 23 Apr 2024 01:39

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Contributors

Author: Adam D. Hart
Author: Andreas Wyttenbach
Author: V. Hugh Perry

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