Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation.
Valeria Lallai, TuKiet T Lam, Rolando Garcia-Milian, Yen-Chu Chen, James P Fowler, Letizia Manca, Daniele Piomelli, Kenneth Williams, Angus C Nairn, Christie D Fowler
Biomolecules September 10, 2024 DOI: 10.3390/biom14091143 via PubMed
Summary
AI-generated from the abstractThe psychoactive component of cannabis, Δ9-tetrahydrocannabinol (THC), alters protein signaling in extracellular vesicles (EVs) in the brain. In cell cultures, THC activated choroid plexus epithelial cells, increasing cannabinoid 1 receptor and c-fos gene expression and releasing RNA-containing EVs. In male and female rats, acute or chronic exposure to aerosolized THC changed the protein composition of brain EVs in cerebrospinal fluid, with effects differing by sex and exposure duration. These results suggest that THC modulates intercellular communication in the brain through EV signaling, offering new insight into how external substances can influence brain signaling.
Study at a glance
| Characteristics | Experimental study with in vitro and in vivo components Peer reviewed |
|---|---|
| Population | Male and female rats |
| Duration | Acute or chronic exposure |
| Topics | Cannabis |
| Keywords | Cerebrospinal fluid Extracellular vesicles Proteomic |
| Key finding | THC exposure alters the protein composition of circulating brain extracellular vesicles in a sex- and exposure-duration-dependent manner. |
Abstract
Given the increasing use of cannabis in the US, there is an urgent need to better understand the drug's effects on central signaling mechanisms. Extracellular vesicles (EVs) have been identified as intercellular signaling mediators that contain a variety of cargo, including proteins. Here, we examined whether the main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), alters EV protein signaling dynamics in the brain. We first conducted in vitro studies, which found that THC activates signaling in choroid plexus epithelial cells, resulting in transcriptional upregulation of the cannabinoid 1 receptor and immediate early gene c-fos, in addition to the release of EVs containing RNA cargo. Next, male and female rats were examined for the effects of either acute or chronic exposure to aerosolized ('vaped') THC on circulating brain EVs. Cerebrospinal fluid was extracted from the brain, and EVs were isolated and processed with label-free quantitative proteomic analyses via high-resolution tandem mass spectrometry. Interestingly, circulating EV-localized proteins were differentially expressed based on acute or chronic THC exposure in a sex-specific manner. Taken together, these findings reveal that THC acts in the brain to modulate circulating EV signaling, thereby providing a novel understanding of how exogenous factors can regulate intercellular communication in the brain.