Microglial Implication in Parkinson's Disease: Loss of Beneficial Physiological Roles or Gain of Inflammatory Functions?

Cynthia Lecours,Marie-Ève Tremblay,Thérèse Di Paolo,Martin Parent,Maude Bordeleau,Léo Cantin

doi:10.3389/fncel.2018.00282

Cynthia Lecours, Marie-Ève Tremblay + Show 4 more

Open Access

https://doi.org/10.3389/fncel.2018.00282

Copy DOI

Abstract

Microglia, often described as the brain-resident macrophages, play crucial roles in central nervous system development, maintenance, plasticity, and adaptation to the environment. Both aging and chronic stress promote microglial morphological and functional changes, which can lead to the development of brain pathologies including Parkinson’s disease (PD). Indeed, aging, and chronic stress represent main environmental risk factors for PD. In these conditions, microglia are known to undergo different morphological and functional changes. Inflammation is an important component of PD and disequilibrium between pro- and anti-inflammatory microglial functions might constitute a crucial component of PD onset and progression. Cumulated data also suggest that, during PD, microglia might lose beneficial functions and gain detrimental ones, in addition to mediating inflammation. In this mini-review, we aim to summarize the literature discussing the functional and morphological changes that microglia undergo in PD pathophysiology and upon exposure to its two main environmental risk factors, aging, and chronic stress.

Highlights

Parkinson’s disease (PD) affects one to two individuals per 1000 (Tysnes and Storstein, 2017), making it the most common neurodegenerative movement disorder (Morin et al, 2014)
Considering that changes in microglial density and morphology profoundly impact on their functions, these findings indicate that microglia could play an important role in PD
Other than the neuroinflammation changes, chronic restraint stress in otherwise healthy rodents was associated with a loss of neurons expressing tyrosine hydroxylase (TH), the enzyme that converts L-DOPA into DA, in the substantia nigra (SN) (Sugama et al, 2016; Ong et al, 2017)

Summary

INTRODUCTION

Parkinson’s disease (PD) affects one to two individuals per 1000 (Tysnes and Storstein, 2017), making it the most common neurodegenerative movement disorder (Morin et al, 2014). Other investigators failed to observe evidence of microglial reactivity in the same region of PD patients (Knott et al, 1999; Mirza et al, 2000) Cytokines such as IL-1β, IL-2, IL-4, IL-6, TNFα, transforming growth factor (TGF)α, and TGFβ1 were increased at the protein level in the striatum, and in the ventricular and lumbar cerebrospinal fluid of PD patients (Vawter et al, 1996; Nagatsu et al, 2000). The authors speculated that microglia might remove distressed motor neurons in PD, through TAM receptor-mediated “phagoptosis” of living neurons causing their death (Brown and Neher, 2012), accelerating PD progression (Fourgeaud et al, 2016) In this case, a beneficial microglial function was proposed to become detrimental upon disease. 6-OHDA mouse model MPTP mouse model Rotenone rat model α-synuclein transgenic mouse model Non-human primate MPTP cynomolgus and rhesus macaque model

AIM scale available to measure LID

CONCLUSION