Work

Delta-9-Tetrahydrocannabinol abrogates neurodegeneration by regulating microbial dysbiosis in transgenic mice expressing gp120 of HIV-1 2631

Year: 2025

Type: article

Abstract: Description AIDS patients develop HIV-associated neurocognitive disorders (HAND), believed to result from neuroinflammation. In this study, we examined the effect of Delta-9-Tetrahydrocannabinol (THC) in HIV gp120 transgenic (Tg) mice and the possible role of the microbiome in causing neurogenesis. For this purpose, wild-type (WT) and gp120Tg mice were treated with either vehicle or THC, and brains were examined for neurogenesis. In gp120 Tg mice, THC treatment reduced reactive gliosis by downregulating the synthesis of gp120 and overexpression of gfap. scRNA sequencing of brain-derived cells demonstrated changes in the microglial subsets, and T cells, with gp120Tg mice expressing low levels of CCR5+ cells, which increased following THC treatment. Treatment of gp120Tg mice with THC led to cAMP-dependent increase in PKA expression. The gut microbiome in gp120Tg mice showed microbial dysbiosis with an increase in pro-inflammatory microbiota while THC-treatment reversed gut dysbiosis. When C57BL/6 wt germ-free (B6gf) mice were transplanted with fecal microbiota from gp120Tg mice (gp120Tg FMT à B6gf mice), they showed neuronal injury by elevating number of CD4+ T cells producing IL-17A and IFN-γ. Our findings demonstrate the critical role of THC in regulating gut microbial dysbiosis and attenuation of neuroinflammation through the gut-brain axis in gp120 Tg mice. Funding Sources This work was supported in part by NIH grants R01ES030144, P01AT003961, P20GM103641, and R01AI123947, R01AI160896 Topic Categories Neuroimmunology (NEUR)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.530