Neuroinflammatory Gene Expression Alterations in Anterior Cingulate Cortical White and Gray Matter of Males With Autism Spectrum Disorder
Abstract
Evidence for putative pathophysiological mechanisms of autism spectrum disorder (ASD), including peripheral inflammation, blood–brain barrier disruption, white matter alterations, and abnormal synaptic overgrowth, indicate a possible involvement of neuroinflammation in the disorder. Neuroinflammation plays a role in the development and maintenance of the dendritic spines involved in glutamatergic and GABAergic neurotransmission, and also influences blood–brain permeability. Cytokines released from microglia can impact the length, location or organization of dendritic spines on excitatory and inhibitory cells as well as recruit and impact glial cell function around the neurons. In this study, gene expression levels of anti‐ and pro‐inflammatory signaling molecules, as well as oligodendrocyte and astrocyte marker proteins, were measured in both gray and white matter tissue in the anterior cingulate cortex from ASD and age‐matched typically developing (TD) control brain donors, ranging from ages 4 to 37 years. Expression levels of the pro‐inflammatory gene, HLA‐DR, were significantly reduced in gray matter and expression levels of the anti‐inflammatory gene MRC1 were significantly elevated in white matter from ASD donors as compared to TD donors, but neither retained statistical significance after correction for multiple comparisons. Modest trends toward differences in expression levels were also observed for the pro‐inflammatory (CD68, IL1β) and anti‐inflammatory genes (IGF1, IGF1R) comparing ASD donors to TD donors. The direction of gene expression changes comparing ASD to TD donors did not reveal consistent findings implicating an elevated pro‐ or anti‐inflammatory state in ASD. However, altered expression of pro‐ and anti‐inflammatory gene expression indicates some involvement of neuroinflammation in ASD. Autism Res 2020, 13: 870‐884. © 2020 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 04, 2020
- Source ID
- 10.1002/aur.2284
Entities
People
- Aubrey N. Sciara
- Brooke Beasley
- Emma P. Anderson
- Gregory A. Ordway
- Jessica D. Crawford
- Michelle J Chandley
- Shimin Zheng
- Tiffani Carrasco
Organizations
- East Tennessee State University
- National Institutes of Health
- United States Department of Defense