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Mediators of Inflammation
Volume 2018, Article ID 7219732, 11 pages
https://doi.org/10.1155/2018/7219732
Review Article

Impact of Aging in Microglia-Mediated D-Serine Balance in the CNS

1Departamento de Neurología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
2Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile

Correspondence should be addressed to Jaime Eugenín; lc.hcasu@ninegue.emiaj and Rommy von Bernhardi; lc.cup.dem@bnovr

Received 9 June 2018; Revised 19 August 2018; Accepted 30 August 2018; Published 27 September 2018

Academic Editor: Marcella Reale

Copyright © 2018 Sebastián Beltrán-Castillo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A mild chronic inflammatory state, like that observed in aged individuals, affects microglial function, inducing a dysfunctional phenotype that potentiates neuroinflammation and cytotoxicity instead of neuroprotection in response to additional challenges. Given that inflammatory activation of microglia promotes increased release of D-serine, we postulate that age-dependent inflammatory brain environment leads to microglia-mediated changes on the D-serine-regulated glutamatergic transmission. Furthermore, D-serine dysregulation, in addition to affecting synaptogenesis and synaptic plasticity, appears also to potentiate NMDAR-dependent excitotoxicity, promoting neurodegeneration and cognitive impairment. D-serine dysregulation promoted by microglia could have a role in age-related cognitive impairment and in the induction and progression of neurodegenerative processes like Alzheimer’s disease.