Diminished circadian rhythms in hippocampal microglia may contribute to age-related neuroinflammatory sensitization

NEUROBIOLOGY OF AGING

卷:47

Article

Fonken, Laura K.¹  Kitt, Meagan M.¹  Gaudet, Andrew D.¹  Barrientos, Ruth M.¹  Watkins, Linda R.¹  Maier, Steven F.¹ 

[1] Univ Colorado, Dept Psychol & Neurosci, Muenzinger Psychol D244,1905 Colorado Ave, Boulder, CO 80309 USA

关键词: Aging;    Neuroinflammation;    Glia;    Priming;    IL-1 beta;   

DOI  :  10.1016/j.neurobiolaging.2016.07.019

来源: Elsevier

【 摘 要 】

Aged animals exhibit diminished circadian rhythms, and both aging and circadian disruption sensitize neuroinflammatory responses. Microglia-the innate immune cell of the central nervous system-possess endogenous timekeeping mechanisms that regulate immune responses. Here, we explored whether aging is associated with disrupted diurnal rhythms in microglia and neuroinflammatory processes. First, hippocampal microglia isolated from young rats (4 months F344XBN) rhythmically expressed circadian clock genes, whereas microglia isolated from the hippocampus of aged rats (25 months) had aberrant Per1 and Per2 rhythms. Unstimulated microglia from young rats exhibited robust rhythms of TNF alpha and IL-1 beta mRNA expression, whereas those from aged rats had flattened and tonically elevated cytokine expression. Similarly, microglial activation markers were diurnally regulated in the hippocampus of young but not aged rats and diurnal differences in responsiveness to both ex vivo and in vivo inflammatory challenges were abolished in aged rats. Corticosterone is an entraining signal for extra-suprachiasmatic nucleus circadian rhythms. Here, corticosterone stimulation elicited similar Per1 induction in aged and young microglia. Overall, these results indicate that aging dysregulates circadian regulation of neuroinflammatory functions. (C) 2016 Elsevier Inc. All rights reserved.

【 授权许可】

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