Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease

NEUROPHARMACOLOGY

卷:96

Review

Norden, Diana M.¹  Muccigrosso, Megan M.¹  Godbout, Jonathan P.^1,2,3 

[1] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA

[2] Ohio State Univ, Inst Behav Med Res, Columbus, OH 43210 USA

[3] Ohio State Univ, Ctr Brain & Spinal Cord Repair, Columbus, OH 43210 USA

关键词: Microglia;    Priming;    Aging;    Traumatic brain injury;    Neurodegenerative disease;    Inflammation;   

DOI  :  10.1016/j.neuropharm.2014.10.028

来源: Elsevier

【 摘 要 】

Glia of the central nervous system (CNS) help to maintain homeostasis in the brain and support efficient neuronal function. Microglia are innate immune cells of the brain that mediate responses to pathogens and injury. They have key roles in phagocytic clearing, surveying the local microenvironment and propagating inflammatory signals. An interruption in homeostasis induces a cascade of conserved adaptive responses in glia. This response involves biochemical, physiological and morphological changes and is associated with the production of cytokines and secondary mediators that influence synaptic plasticity, cognition and behavior. This reorganization of host priorities represents a beneficial response that is normally adaptive but may become maladaptive when the profile of microglia is compromised. For instance, microglia can develop a primed or pro-inflammatory mRNA, protein and morphological profile with aging, traumatic brain injury and neurodegenerative disease. As a result, primed microglia exhibit an exaggerated inflammatory response to secondary and sub-threshold challenges. Consequences of exaggerated inflammatory responses by microglia include the development of cognitive deficits, impaired synaptic plasticity and accelerated neurodegeneration. Moreover, impairments in regulatory systems in these circumstances may make microglia more resistant to negative feedback and important functions of glia can become compromised and dysfunctional. Overall, the purpose of this review is to discuss key concepts of microglial priming and immune-reactivity in the context of aging, traumatic CNS injury and neurodegenerative disease. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

Free