Δ9-THC increases endogenous AHA1 expression in rat cerebellum and may modulate CB1 receptor function during chronic use.
Catalin M Filipeanu, Jesse J Guidry, Stuart T Leonard, Peter J Winsauer
Journal of Neurochemistry September 2011 DOI: 10.1111/j.1471-4159.2011.07391.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study with in vitro cell experiments Peer reviewed |
|---|---|
| Population | Adult female rats treated with Δ9-THC during adolescence, with and without ovariectomy; HEK293T and Neuro-2A cell lines |
| Interventions | Δ9-THC ovariectomy AHA1 over-expression |
| Duration | 40 days of Δ9-THC treatment during adolescence |
| Topics | Cannabis |
| Key findings | Chronic Δ9-THC administration during adolescence altered cerebellar levels of six proteins, decreasing pyruvate carboxylase and NADH dehydrogenase and increasing NM23B, translationally controlled tumor protein, DJ-1, and AHA1, with ovariectomy also lowering the mitochondrial proteins. AHA1 over-expression increased CB1R cell-surface levels and CB1R-mediated cAMP and MAPK signaling but did not affect CB2R localization or signaling, suggesting AHA1 can regulate CB1R trafficking and signaling. |
Abstract
To characterize the long-term effects of adolescent marijuana abuse, we performed a proteomic analysis of cerebellar extracts from adult female rats with and without ovariectomy that were treated with Δ9-THC for 40 days during adolescence. Six proteins were found to significantly differ among the four treatment groups, with Δ9-THC and ovariectomy (OVX) decreasing the mitochondrial proteins, pyruvate carboxylase and NADH dehydrogenase, whereas the levels of putative cytosolic molecular chaperones NM23B, translationally controlled tumor protein, DJ-1 and activator of heat-shock 90kDa protein ATPase homolog 1 (AHA1) were increased. We further analyzed the effects of AHA1, a HSP90 co-chaperone, on CB1R and CB2R trafficking and signaling in transfected HEK293T and Neuro-2A cells. In HEK293T cells, AHA1 over-expression enhanced plasma membrane levels of CB1R and increased CB1R-mediated effects on cAMP levels and on MAPK phosphorylation. AHA1 over-expression also enhanced cell surface levels of endogenous CB1R and the effects of Δ9-THC on the cAMP levels in Neuro-2A cells. In contrast, over-expression of AHA1 did not affect the subcellular localization and signaling of CB2R. Our data indicate that chronic Δ9-THC administration in adolescence altered the endogenous levels of specialized proteins in the cerebellum, such as AHA1, and that this protein can change CB1R cell surface levels and signaling.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 2
- A Proteomic View of Cellular and Molecular Effects of Cannabis Biomolecules September 27, 2021
- Ovarian hormones and chronic administration during adolescence modify the discriminative stimulus effects of delta-9-tetrahydrocannabinol (Δ⁹-THC) in adult female rats. Pharmacology, Biochemistry, and Behavior September 2012