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HIV and ART Disruptions in Glial Cell Lipid Metabolism and its Effect on Adolescent Myelination

Award Number: F32MH135724
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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HIV and ART Disruptions in Glial Cell Lipid Metabolism and its Effect on Adolescent Myelination - PROJECT SUMMARY/ABSTRACT Human immunodeficiency virus (HIV) infections are dramatically climbing in adolescents, who are infected during a time of critical brain development characterized by significant myelination. Adolescents may therefore be particularly vulnerable to the white matter pathologies closely linked to HIV-associated neurocognitive disorders (HAND), which affect 30-50% of people living with HIV. Understanding the mechanisms resulting in HIV-related white matter deficits will be key in the development of therapies to promote myelin integrity and repair, which may greatly improve neurological function. One important factor predictive of both cognitive decline in HIV and a lack of myelin is altered brain lipid metabolism. Myelin is highly enriched in cholesterol and lipids, and both oligodendrocytes, the myelin-producing glial cells of the central nervous system, and astrocytes must synthesize large quantities of cholesterol and lipids for successful myelination to occur. Based on published and preliminary data, I hypothesize that glial lipid biosynthesis and transport essential for adolescent myelination are dysregulated by HIV or DTG/TDF/FTC antiretroviral therapy (ART), making lipid metabolism a potential therapeutic target for improving white matter integrity in adolescents living with HIV. To address this hypothesis, I will determine how HIV and ART affect 1) oligodendroglial lipid metabolism and resulting myelin lipid composition and adolescent myelination, and 2) astroglial lipid metabolism and release and its impact on myelin formation. Successful completion of the proposed aims will reveal whether HIV or ART affect lipid metabolism in either oligodendrocytes and/or astrocytes and whether this is detrimental to adolescent myelination. Results from the proposed studies will directly advance the mission of the NIMH by transforming our understanding of mechanisms of white matter pathology in adolescent HIV/HAND, revealing potential therapeutic targets for prevention of and recovery from HIV-related neuropathology.


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: 2026 ( Subtotal = $89,848 )
2026	2026	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	3	4/10/2026	NON-COMPETING CONTINUATION	$89,848
														Subtotal = $89,848

Issue Date FY: 2025 ( Subtotal = $85,924 )
2025	2025	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	2	3/6/2025	NON-COMPETING CONTINUATION	$84,592
2025	2025	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	001	2	9/8/2025	NON-COMPETING CONTINUATION	$1,332
														Subtotal = $85,924

Issue Date FY: 2024 ( Subtotal = $82,456 )
2024	2024	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	001	1	2/26/2024	NEW	$0
2024	2024	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	1	2/26/2024	NEW	$76,992
2024	2024	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	002	1	8/7/2024	NEW	$5,464
														Subtotal = $82,456

Grand Total All Awards = $258,228

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HIV and ART Disruptions in Glial Cell Lipid Metabolism and its Effect on Adolescent Myelination

Award Number: F32MH135724

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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