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

> **NIH NIH R56** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $520,624

## 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 β-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.

## Key facts

- **NIH application ID:** 10450981
- **Project number:** 1R56NS124478-01
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Dianne Teresa LANGFORD
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $520,624
- **Award type:** 1
- **Project period:** 2021-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450981

## Citation

> US National Institutes of Health, RePORTER application 10450981, HIV and cocaine use leads to loss of astrocyte neurotrophic support and impaired lipid homeostasis in the brain (1R56NS124478-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10450981. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*