Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

Brain lipid rafts in cholesterol biosynthesis disorders  

Autism is a neurodevelopmental disorder of complex etiology. Emerging evidence suggests that low cholesterol levels due to defective cholesterol synthesis may play a role in the pathogenesis of autism or autism spectrum disorder (ASD). Cholesterol biosynthesis is essential for brain development because, in contrast to most other organs, the brain must make its own cholesterol from the early embryonic stage. Thus, deficiency in cholesterol production in the brain during embryogenesis may lead to faulty neurodevelopment. The role of cholesterol in the organization and function of lipid rafts, the specialized structural and functional domains in cell membranes, is a fundamental question in biology. Brain cholesterol biosynthetic defects may lead to disorganization of lipid rafts in developing brain, and cause brain abnormalities. In this study, the investigators will delineate the effects of defective cholesterol synthesis on the organization of lipid rafts in the developing brain and the associated pathophysiological consequences. To address these questions, they will employ the genetic mouse models of 3¿-hydroxysterol-¿24 reductase (Dhcr24) and 3¿-hydroxysterol-¿7 reductase (Dhcr7) deficiencies, because these two models represent disruption of two obligatory pathways of cholesterol synthesis. In order to develop an integrated understanding of lipid raft formation in the developing brain and to identify the potential disease-associated biomarkers and disturbed pathways, the investigators will conduct comprehensive analyses of the raft protein and lipid compositions in Dhcr24-deficient and Dhcr7-deficient brains by quantitative proteomics and lipidomics approaches. The proposed research will help to gain further insight into the mechanisms of the membrane defects caused by disruption of cholesterol biosynthesis, and also will shed new light on the potential role of more subtle abnormalities in cholesterol synthesis in ASD. Project Status
NEW

2010

Funder National Institutes of Health
Fiscal Year Funding $63,000.00
Current Award Period 2010-2012
Project Number 1R03HD062938-01
Principal Investigator Yu, Hongwei
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Molecular Pathways
Strategic Plan Objective 2O. Not specific to Question 2 objectives
Federal or Private? Federal
Institution Medical College of Wisconsin
State/Country Wisconsin
Web Link 1 Brain lipid rafts in cholesterol biosynthesis disorders (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects Not available at this time. This functionality is experimental.