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

Prostaglandins and cerebellum development  

Autism spectrum disorder (ASD) and schizophrenia are neuropsychiatric diseases with origins in development, genetics and the environment. Understanding how environmental influences converge with genetic predispositions during specific developmental windows to create a sensitive period is the key to discovering the etiology of and potential therapeutic treatments for these complex disorders. This proposal explores how a specific environmental influence, inflammation and the medications that treat it, can selectively alter brain development and create vulnerability where none existed. Using the laboratory rat, this research will investigate the novel concept that inflammation during a restricted sensitive period leads to excess prostaglandin E2 (PGE2), a proinflammatory molecule that stimulates aromatase activity and estradiol synthesis locally within the cerebellum. Excessive estradiol stunts the outgrowth of Purkinje neuron dendrites by up-regulating GABA (gamma amino-butyric acid) synthesis. Conversely, exposure to anti-inflammatory medications such as NSAIDs (non-steroidal anti-inflammatory drugs) or acetominophen has the opposite effect, causing exuberant dendritic sprouting. The data generated by these experiments will highlight a previously unexpected source of risk for developmental neuropsychiatric disease, prostaglandins elevated during inflammation and/or the frequently used medications designed to block inflammation. Understanding how inflammation and the medications taken to treat it impact the developing cerebellum will provide important mechanistic insight into the origins of these disorders of mental health. Project Status


Funder National Institutes of Health
Fiscal Year Funding $375,000.00
Current Award Period 2010-2015
Project Number 1R01MH091424-01
Principal Investigator McCarthy, Margaret
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Immune/Metabolic Pathways
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 2SA. Support at least four research projects to identify mechanisms of fever, metabolic and/or immune system interactions with the central nervous system that may influence ASD during prenatal-postnatal life by 2010. IACC Recommended Budget: $9,800,000 over 4 years. (Fever studies to be started by 2012.)
Federal or Private? Federal
Institution University of Maryland, Baltimore
State/Country Maryland
Web Link 1 Prostaglandins and cerebellum development (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects N/A