Microglia of the Aged Brain: Primed to be Activated and Resistant to Regulation

By Diana M. Norden, Jonathan P. Godbout. Neuropathology and Applied Neurobiology, 2013

753 citations recorded by the source corpus.

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.

Subfields: Biological Psychiatry, Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/7327e08817ce58d14862376aa91a9315643cee07

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Citations in the corpus

Microglia induce motor neuron death via the classical NF-κB pathway in amyotrophic lateral sclerosis (2014, positive): “Interestingly, we observed an increase in CD68 and CD86-positive microglia in 8 month WT controls compared to 4 month-old controls, which supports previous reports that microglial activation increases with aging (Norden and Godbout, 2013).”
The biphasic function of microglia in ischemic stroke (2017, neutral): “Furthermore, microglia polarization could be affected by the time and severity of injury, aging, and microenvironment (Hu et al., 2015; Norden and Godbout, 2013; Perego et al., 2011).”
Neuroinflammation: The Devil is in the Details (2016, positive): “Nonetheless, amplified, exaggerated, or chronic microglial activation can lead to robust pathological changes and neurobehavioral complications such as depression and cognitive deficits (Norden and Godbout 2013).”
Microglia: Dynamic Mediators of Synapse Development and Plasticity (2015, background): “While these changes have been investigated in the context of neuroinflammation or immune challenge to the CNS [54], the effects on synaptic structure and function in the non-inflamed brain is still relatively mysterious.”
Normal aging induces A1-like astrocyte reactivity (2018, background): “Consistent with the observed transcriptional changes, there is evidence that microglia adopt an activated morphology in aged brains (17).”