Relevance of chronic stress and the two faces of microglia in Parkinson's disease.

Antonio J Herrera,Alberto García-Quintanilla,Ana M Espinosa-Oliva,Rocío M De Pablos,Juan García-Revilla,María J Oliva-Martín,José L Venero,Alejandro Carrillo-Jiménez

doi:10.3389/fncel.2015.00312

Abstract

This review is aimed to highlight the importance of stress and glucocorticoids (GCs) in modulating the inflammatory response of brain microglia and hence its potential involvement in Parkinson’s disease (PD). The role of inflammation in PD has been reviewed extensively in the literature and it is supposed to play a key role in the course of the disease. Historically, GCs have been strongly associated as anti-inflammatory hormones. However, accumulating evidence from the peripheral and central nervous system have clearly revealed that, under specific conditions, GCs may promote brain inflammation including pro-inflammatory activation of microglia. We have summarized relevant data linking PD, neuroinflamamation and chronic stress. The timing and duration of stress response may be critical for delineating an immune response in the brain thus probably explain the dual role of GCs and/or chronic stress in different animal models of PD.

Highlights

This review is aimed to highlight the importance of stress and glucocorticoids (GCs) in modulating the inflammatory response of brain microglia and its potential involvement in Parkinson’s disease (PD)
We have summarized relevant data linking PD, neuroinflamamation and chronic stress
Parkinson’s disease (PD) is a neurodegenerative disorder second only to Alzheimer’s disease (AD) in prevalence. It is characterized by the loss of the dopaminergic neurons in the substantia nigra (SN) and the accumulation of α-synuclein (α-syn) and other proteins in intracellular proteinaceous aggregates called Lewy bodies (LB)

Summary

Introduction

This review is aimed to highlight the importance of stress and glucocorticoids (GCs) in modulating the inflammatory response of brain microglia and its potential involvement in Parkinson’s disease (PD). Accumulating evidence from the peripheral and central nervous system have clearly revealed that, under specific conditions, GCs may promote brain inflammation including pro-inflammatory activation of microglia. Idiopathic forms, usually affecting people from 65 years old, have an obscure etiology; mitochondrial dysfunction, toxins, oxidative stress, infections, decrease of trophic factors, impairment of the ubiquitine-proteosome system, metabolic alterations, inflammation and the accumulative effect of a number of susceptibility genes have been proposed to explain the initiation and development of this form, which accounts for 95% of cases. Considering the Inflammation and stress in Parkinson’s disease brain was believed to have immune privilege,these inflammatory signs were thought to be a response from the microglial system to neuronal death. The brain is no longer considered to be immunoprivileged; infiltration of lymphocytes into the brain parenchyma of PD patients has been demonstrated (Brochard et al, 2009); the role of T lymphocytes in PD will be reviewed in ‘‘Chronic Stress and Parkinson’s Disease in Humans’’ Section)

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Conclusion