Cocaine Upregulates Microglial Lipid Droplet Formation Through Increasing Lipid Synthesis Activity In Vitro and In
Yan Cheng1, Brooke Russell1, Liam Liyang Guo2
1Department of Biological and Translational, Macon and Joan Brock Eastern Virginia Medical School/Virginia Health Sciences, Old Dominion University, Norfolk, VA 23507, USA.
Biomolecules
|May 4, 2026
Summary
Cocaine use promotes lipid droplet accumulation microglia (LDAMs) formation in the brain, worsening brain aging and neurodegenerative disease risks. Targeting microglial lipid metabolism may offer new treatments for cocaine addiction-related neurological issues.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Lipid droplet accumulation microglia (LDAMs) are linked to brain aging and neurodegeneration.
- Cocaine alters brain lipidomics, activates microglia, and accelerates brain aging.
Purpose of the Study:
- To investigate cocaine's impact on microglial lipid metabolism.
- To determine if cocaine affects LDAM formation and associated aging pathways.
Main Methods:
- Chronic cocaine administration in vivo and in vitro experiments with microglia (BV2 and primary).
- Analysis of brain lipid profiles, LDAM quantification, and senescence marker (p53) expression.
- Investigation of key lipid synthesis pathway regulators (SREBP1/2, HMGCR, DGAT1, FASN).
Main Results:
- Cocaine administration increased LDAM formation in vivo and in vitro.
- Elevated LDAMs correlated with increased p53, a senescence marker.
- Cocaine upregulated critical lipid synthesis enzymes, including SREBP1/2, HMGCR, DGAT1, and FASN.
Conclusions:
- Cocaine promotes LDAM formation by enhancing lipid synthesis pathways.
- Microglial lipid metabolism is a potential therapeutic target for mitigating cocaine addiction-related neurological aging.
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