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THC Reverses SIV-Induced Senescence in Astrocytes: Possible Compensatory Mechanism Against HIV Associated Brain
Biorxiv : the Preprint Server for Biology
|June 6, 2025
Summary
Tetrahydrocannabinol (THC) may help reduce neuroinflammation in people living with HIV by protecting astrocytes and lowering inflammatory cytokines. However, high doses might harm glial cells, showing complex effects of cannabinoids.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Chronic neuroinflammation and glial dysfunction persist in people living with HIV (PLWH) despite combination antiretroviral therapy (cART).
- The endocannabinoid system is a potential therapeutic target for neuroimmune modulation.
- The influence of cannabinoids on HIV-associated neuroinflammation requires further investigation.
Purpose of the Study:
- To investigate the impact of Δ9-tetrahydrocannabinol (THC) on astrocyte characteristics and cytokine release when exposed to HIV Tat protein.
- To assess THC's effects on glial cell viability, morphology, and inflammatory responses in primary mixed glial cultures from rhesus macaques.
Main Methods:
- Primary mixed glial cultures from rhesus macaques were exposed to HIV Tat protein and varying doses of THC.
- Cellular integrity was monitored using real-time impedance (xCELLigence system).
- Morphological changes and cytokine secretion (TNF-α, IL-6, IL-1β) were analyzed via microscopy and multiplex immunoassays.
Main Results:
- THC protected astrocytes from Tat-induced senescence and improved adhesion recovery.
- THC promoted glial process elongation and morphological complexity, suggesting a shift to a neuroprotective phenotype.
- THC significantly reduced the secretion of inflammatory cytokines (TNF-α, IL-6, IL-1β) in a dose-dependent manner.
Conclusions:
- THC may mitigate HIV-associated neuroinflammation by enhancing astrocyte survival, reducing inflammatory cytokines, and promoting neurotrophic signaling.
- Cannabinoid signaling in the central nervous system (CNS) is complex, with potential risks at high doses.
- Cannabinoid-based interventions show promise for managing neuroinflammation in PLWH.
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