Document Detail

Review: microglia of the aged brain: primed to be activated and resistant to regulation.
MedLine Citation:
PMID:  23039106     Owner:  NLM     Status:  MEDLINE    
Innate immunity within the central nervous system (CNS) is primarily provided by resident microglia. Microglia are pivotal in immune surveillance and also facilitate the co-ordinated responses between the immune system and the brain. For example, microglia interpret and propagate inflammatory signals that are initiated in the periphery. This transient microglial activation helps mount the appropriate physiological and behavioural response following peripheral infection. With normal ageing, however, microglia develop a more inflammatory phenotype. For instance, in several models of ageing there are increased pro-inflammatory cytokines in the brain and increased expression of inflammatory receptors on microglia. This increased inflammatory status of microglia with ageing is referred to as primed, reactive or sensitized. A modest increase in the inflammatory profile of the CNS and altered microglial function in ageing has behavioural and cognitive consequences. Nonetheless, there are major differences in microglial biology between young and old age when the immune system is challenged and microglia are activated. In this context, microglial activation is amplified and prolonged in the aged brain compared with adults. The cause of this amplified microglial activation may be related to impairments in several key regulatory systems with age that make it more difficult to resolve microglial activation. The consequences of impaired regulation and microglial hyper-activation following immune challenge are exaggerated neuroinflammation, sickness behaviour, depressive-like behaviour and cognitive deficits. Therefore the purpose of this review is to discuss the current understanding of age-associated microglial priming, consequences of priming and reactivity, and the impairments in regulatory systems that may underlie these age-related deficits.
D M Norden; J P Godbout
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Neuropathology and applied neurobiology     Volume:  39     ISSN:  1365-2990     ISO Abbreviation:  Neuropathol. Appl. Neurobiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-07-24     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  7609829     Medline TA:  Neuropathol Appl Neurobiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  19-34     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.
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MeSH Terms
Aging / immunology*
Brain / immunology*
Immunity, Innate / immunology
Inflammation / immunology*
Microglia / immunology*
Grant Support
R01 AG033028/AG/NIA NIH HHS; R01-AG-033028/AG/NIA NIH HHS

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