UH Researchers Advance Understanding of Autism
Two 葫芦影业 scientists are reporting that defects in a portion of the brain鈥檚 hippocampus, called the dentate gyrus, are regulated by the nuclear receptor LXR尾 (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).
Margaret Warner, professor of biology and biochemistry, and Jan-脜ke Gustafsson, professor of biology and biochemistry and founding director of the UH Center for Nuclear Receptors and Cell Signaling, describe the work in the .
For four decades they have worked together, making discovery after discovery about the role of nuclear receptors in brain functions, and they show no sign of slowing down.
Tracking Down the Culprit
Neurogenesis, or the regulation of growth of the dentate gyrus, occurs prenatally and postnatally.
鈥淥ur 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,鈥� Warner said.
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 LXR尾 have emerged as the possible culprit of defects in the DG.
Why this Gray Matter Matters
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, LXR尾, may be the one that holds the key to the genesis of autism. Warner and Gustafsson established this the only way they could 鈥� by taking LXR尾 out of the equation.
鈥淜nocking out LXR尾 led to autistic behavior and reduced cognitive flexibility,鈥� Warner said. 鈥淚n this paper, we share our findings that that deletion of the LXR尾 causes hypoplasia or underdevelopment in the DG and autistic-like behaviors, including abnormal social interaction and repetitive behavior.鈥�
They went on to report: 鈥淭he behavioral studies confirmed that ablation of LXR尾 caused behavior disorders relevant to major ASD symptoms. Social interaction deficits, as key phenotypic traits of ASD, were evident鈥︹��
Gustafsson said the findings are the path forward in autism research.
鈥淭he Liver X receptor Beta is important in the dentate gyrus and in autism, and more studies on the receptor are going to help us cure or treat autism,鈥� he said.
He should know. He鈥檚 the scientist who discovered LXR尾 in 1996.
鈥淯ntil 1996, we did not know that this receptor even existed, and it is so important in brain function,鈥� Warner said.
On the project, the UH team includes Wanfu Wu, a research assistant professor. They are joined by Yulong Cai, Xiaotong Tang, Xin Li, Ying Wang, Xiaohang Bao, Lian Wang, Dayu Sun, Jinghui Zhao, Yan Xing, Xiaotang Fan and Haiwei Xu from Third Military Medical University in Chongqing, China.
- Laurie Fickman, University Media Relations