Citation

Norden DM, Muccigrosso MM, Godbout JP. Neuropharmacology 2014; 96(Pt A): 29-41.

Affiliation

Department of Neuroscience, The Ohio State University, 333 W. 10(th) Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Dr., Columbus, OH 43210, USA; Center for Brain and Spinal Cord Repair, The Ohio State University, 460 W. 12(th) Ave, Columbus, OH 43210, USA. Electronic address: Jonathan.Godbout@osumc.edu.

Copyright

(Copyright © 2014, Elsevier Publishing)

DOI

10.1016/j.neuropharm.2014.10.028

PMID

25445485

Abstract

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.

Language: en