Nuclear receptor defects in the brain linked to autism spectrum disorders

Nuclear receptor defects in the brain linked to autism spectrum disorders


Scientists report that defects in a portion of the brain's hippocampus, called the dentate gyrus, is regulated by the nuclear receptor LXRβ (Liver X receptor Beta). The dentate gyrus, or DG, is responsible for emotion and memory and is known to be involved in autism spectrum disorders (ASD).

Neurogenesis, or the regulation of growth of the dentate gyrus, occurs prenatally and postnatally.

"Our findings suggest early changes in DG neurogenesis ultimately provide an aberrant template upon which to build the circuitry that is involved in normal social function," said the author.

Their studies propose that defects in the neurogenesis of the DG seem to be involved in the etiology of autism spectrum disorders and their associated behaviors. Specifically, defects in the nuclear receptor LXRβ has emerged as the possible culprit of defects in the DG.

In the world of physiology (how the organisms in our bodies communicate and keep us alive), nuclear receptors rule the day. They are a class of proteins within cells that control hormones and regulate metabolism. One of these proteins, LXRβ, may be the one that holds the key to the genesis of autism. Researchers established this the only way they could - by taking LXRβ out of the equation.

"Knocking out LXRβ led to autistic behavior and reduced cognitive flexibility," said the author. "In this paper we share our findings that that deletion of the LXRβ causes hypoplasia or underdevelopment in the DG and autistic-like behaviors, including abnormal social interaction and repetitive behavior."

Abnormalities include formation of progenitor cells and granule cell differentiation. Authors  also found that expression of Notch1, a central mediator of progenitor cell self-renewal, is reduced in LXRβ-null mice.

They went on to report: "The behavioral studies confirmed that ablation of  caused behavior disorders relevant to major ASD symptoms. Social interaction deficits, as key phenotypic traits of ASD, were evident..." another author said the findings are the path forward in autism research.

http://www.uh.edu/news-events/stories/2018/march-2018/031418-autism-brain-gustaffson-warner.php

http://www.pnas.org/content/early/2018/02/28/1800184115

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