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The Impact of Vitamin D on mTOR Signaling, Seizures, and Motor Behavior in a Mouse Model of Hyperactive mTOR Induced Epilepsy and Ataxia

Award Number: F99NS134141
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Project Summary / Abstract Increased mammalian target of rapamycin (mTOR) signaling is a known cause of treatment resistant epilepsy. Pathological mutations to negative regulators of mTOR lead to hyperactive mTOR signaling and have been found in the forebrain and cerebellum of individuals with epilepsy. The cerebellum has recently been shown to contribute to the development of epilepsy. However, research in hyperactive mTOR induced epilepsy has almost exclusively been focused on the hypothalamus and forebrain structures. Individuals that develop seizures associated with hyperactive mTOR in the cerebellum are often resistant to pharmacological intervention and require invasive brain surgery. In severe cases, surgery can fail to control growth and must be repeated. Thus novel treatments are critically needed. Preliminary data show supplemental vitamin D may suppress epilepsy in a mouse model of hyperactive mTOR induced epilepsy and ataxia. This proposal aims to determine whether vitamin D supplementation beginning during adolescence reduces seizures and co- occurring motor impairments (Aim 1A), restores mTOR signaling in adulthood in a rodent model of hyperactive mTOR induced epilepsy and ataxia (Aim 1B) and reverses cerebellar granule cell hypertrophy (Aim 1C). The F99 phase of this fellowship will provide expertise and training in examining the molecular mechanisms underlying genetic causes of neurological disorders and in the testing of novel mechanisms of pharmaceutical therapies. The completion of the F99 phase will provide training that will serve as a springboard for the K00 phase. Baylor University possesses a strong molecular biosciences and imaging core, a dedicated graduate writing center, and faculty and seminars devoted to professional training and teaching. The enclosed proposal for the F99 and K00 phases outlines the training plan for a successful transition from a pre-doctoral trainee to an independent investigator examining treatments for neurodevelopmental disorders.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $44,325 )
2023	2023	BAYLOR UNIVERSITY	700 S UNIVERSITY PARKS DR	WACO	TX	76706	MCLENNAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/30/2023	NEW	$44,325
														Subtotal = $44,325

Grand Total All Awards = $44,325

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The Impact of Vitamin D on mTOR Signaling, Seizures, and Motor Behavior in a Mouse Model of Hyperactive mTOR Induced Epilepsy and Ataxia

Award Number: F99NS134141

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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