Brain Inflammation A Hallmark Of Autism, Large-Scale Analysis Shows
Johns Hopkins study is largest so far of gene expression in autism brains
Release Date: December 10, 2014
While many different combinations of genetic traits can cause autism, brains affected by autism share a pattern of ramped-up immune responses, an analysis of data from autopsied human brains reveals.
“There are many different ways of getting autism, but we found that they all have the same downstream effect,” says Dan Arking, Ph.D., an associate professor in the McKusick-Nathans Institute for Genetic Medicine at the Johns Hopkins University School of Medicine. “What we don’t know is whether this immune response is making things better in the short term and worse in the long term.”
Lees meer Bron: JohnsHopkinsMedicine
Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism
Simone Gupta, Shannon E. Ellis, Foram N. Ashar, Anna Moes, Joel S. Bader, Jianan Zhan, Andrew B. West & Dan E. Arking
Nature Communications 5, Article number: 5748 doi:10.1038/ncomms6748
Published 10 December 2014
Recent studies of genomic variation associated with autism have suggested the existence of extreme heterogeneity. Large-scale transcriptomics should complement these results to identify core molecular pathways underlying autism. Here we report results from a large-scale RNA sequencing effort, utilizing region-matched autism and control brains to identify neuronal and microglial genes robustly dysregulated in autism cortical brain. Remarkably, we note that a gene expression module corresponding to M2-activation states in microglia is negatively correlated with a differentially expressed neuronal module, implicating dysregulated microglial responses in concert with altered neuronal activity-dependent genes in autism brains. These observations provide pathways and candidate genes that highlight the interplay between innate immunity and neuronal activity in the aetiology of autism.
Lees meer Bron: Nature
