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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

Prostaglandins and cerebellum development

Principal Investigator

Principal Investigator

McCarthy, Margaret

Description

Description

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.

Funder

Funder

National Institutes of Health

Fiscal Year Funding

Fiscal Year Funding

371250

Current Award Period

Current Award Period

2010-2015

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

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.)

Project Link

Project Link

Prostaglandins and cerebellum development (External web link)

Institution

Institution

University of Maryland, Baltimore

State/Country

State/Country

Maryland

Project Number

Project Number

5R01MH091424-03

Federal or Private?

Federal or Private?

Federal

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Prostaglandins and cerebellum development | 371250 | 2011 | 5R01MH091424-02

 
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