Thursday, April 25, 2024 4/25/2024

HIV and cocaine use leads to loss of astrocyte neurotrophic support and impaired lipid homeostasis in the brain

Award Number: R01NS124478
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Summary Tight metabolic coupling between astrocytes and neurons involves astrocytes sensing neuronal stress and responding by taking up lipid-like particles containing excess peroxidated fatty acids (FA) generated during stress. During stressful conditions, the generation of reactive oxygen species (ROS) induce the peroxidation of FA in neurons. Neurons are highly sensitive to toxic peroxidated FA and unlike astrocytes, neurons have a low capacity to form lipid droplets (LD) to encase the toxic FA. Moreover, neuronal mitochondria are unable to efficiently consume FAs as an energy source. Thus, neurons expel lipid-like particles carrying the FAs. Astrocytes endocytose lipid-like particles with FA, deliver them to the ER for packaging into lipid droplets (LD) to protect the cell from the toxic FAs. LD also provide a conduit for delivery of FA to astrocyte mitochondria for use as an alternative energy source during stress. In normal conditions, astrocytes use glucose rather than FA as their main source of reserve energy under normal conditions. Metabolic coordination between astrocytes and neurons is critical for CNS functioning and lipid homeostasis. However, changes in astrocyte-neuron coupling for lipid metabolism in response to HIV and cocaine use is unknown. It is known that toxic, peroxidated fatty acids (FAs) produced and expelled by stressed neurons are transferred to astrocytic lipid droplets (LD) by lipoprotein particles. Astrocytes consume the FAs stored in LD via mitochondrial ß-oxidation. Thus, metabolism of neuron-derived FA metabolism by astrocytes protects neurons from FA toxicity. Disruption of this tightly coordinated coupling to metabolize FAs likely contributes to the increased astrocytic energy metabolism and neuronal deficit reported during detrimental synergy between HIV infection and cocaine use.


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: 2024 ( Subtotal = $391,607 )
2024	2022	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/8/2024	NEW	$391,607
														Subtotal = $391,607

Issue Date FY: 2023 ( Subtotal = $628,590 )
2023	2023	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	9/6/2023	NON-COMPETING CONTINUATION	$628,590
2023	2022	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/6/2023	NEW	$0
														Subtotal = $628,590

Issue Date FY: 2022 ( Subtotal = $643,897 )
2022	2022	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/20/2022	NEW	$643,897
														Subtotal = $643,897

Grand Total All Awards = $1,664,094

Top

All Categories

About

Search

Reports

Data Submission

Award Information

HIV and cocaine use leads to loss of astrocyte neurotrophic support and impaired lipid homeostasis in the brain

Award Number: R01NS124478

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer