[Delta]9-THC increases endogenous AHA1 expression in rat cerebellum and may modulate CB1 receptor function during chronic use
J. Neurochem. (2011) 118, 1101-1112. 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 40days during adolescence. Six proteins we...
Saved in:
Published in | Journal of neurochemistry Vol. 118; no. 6; p. 1101 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
New York
Blackwell Publishing Ltd
01.09.2011
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | J. Neurochem. (2011) 118, 1101-1112. 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 40days 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. |
---|---|
ISSN: | 0022-3042 1471-4159 |
DOI: | 10.1111/j.1471-4159.2011.07391.x |