L'amorçage développemental microglial dans le cortex temporel post-mortem dans le spectre de l'autisme

Aperçu: G.M.

La microglie peut se transformer en différentes morphologies complexes en fonction du microenvironnement du système nerveux central (SNC). Les morphologies distinctes sont en corrélation avec des fonctions spécifiques et peuvent indiquer l'état pathophysiologique du SNC. Les études post-mortem antérieures du trouble du spectre autistique (ASD) ont montré une neuroinflammation dans les TSA indiquée par une augmentation de la densité microgliale.Ces changements dans la densité de la microglie peuvent s'accompagner de changements dans le phénotype de la microglie mais la contribution individuelle des différents phénotypes de la microglie à la pathophysiologie des TSA reste incertaine. 

Les résultats témoignent d'un changement dans le phénotype microglial qui peut indiquer une plasticité synaptique altérée et une vulnérabilité chronique aux réponses immunitaires exagérées. 

Brain Behav Immun. 2017 May;62:193-202. doi: 10.1016/j.bbi.2017.01.019. Epub 2017 Feb 1.

Developmental microglial priming in postmortem autism spectrum disorder temporal cortex

Lee AS¹, Azmitia EC², Whitaker-Azmitia PM³.

Author information

1

Department of Psychology, Stony Brook University, Stony Brook, NY 11794, USA; Department of Biology, New York University, New York, NY 10003, USA; Max Planck Institute for Biological Cybernetics, 72076 Tuebingen, Germany. Electronic address: Andrew.s.lee@alumni.stonybrook.edu

2

Department of Biology, New York University, New York, NY 10003, USA.

3

Department of Psychology, Stony Brook University, Stony Brook, NY 11794, USA.

Abstract

Microglia can shift into different complex morphologies depending on the microenvironment of the central nervous system (CNS). The distinct morphologies correlate with specific functions and can indicate the pathophysiological state of the CNS. Previous postmortem studies of autism spectrum disorder (ASD) showed neuroinflammation in ASD indicated by increased microglial density. These changes in the microglia density can be accompanied by changes in microglia phenotype but the individual contribution of different microglia phenotypes to the pathophysiology of ASD remains unclear. Here, we used an unbiased stereological approach to quantify six structurally and functionally distinct microglia phenotypes in postmortem human temporal cortex, which were immuno-stained with Iba1. The total density of all microglia phenotypes did not differ between ASD donors and typically developing individual donors. However, there was a significant decrease in ramified microglia in both gray matter and white matter of ASD, and a significant increase in primed microglia in gray matter of ASD compared to typically developing individuals. This increase in primed microglia showed a positive correlation with donor age in both gray matter and white of ASD, but not in typically developing individuals. Our results provide evidence of a shift in microglial phenotype that may indicate impaired synaptic plasticity and a chronic vulnerability to exaggerated immune responses.

Copyright © 2017 Elsevier Inc. All rights reserved.

PMID: 28159644

DOI: 10.1016/j.bbi.2017.01.019