Role of Sigma Receptor in Cocaine-Mediated Induction of Glial Fibrillary Acidic Protein: Implications for HAND.
Title | Role of Sigma Receptor in Cocaine-Mediated Induction of Glial Fibrillary Acidic Protein: Implications for HAND. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Yang, L, Yao, H, Chen, X, Cai, Y, Callen, S, Buch, S |
Journal | Mol Neurobiol |
Volume | 53 |
Issue | 2 |
Pagination | 1329-1342 |
Date Published | 2016 Mar |
ISSN | 1559-1182 |
Keywords | Adult, AIDS Dementia Complex, Animals, Astrocytes, Cocaine, Cocaine-Related Disorders, Early Growth Response Protein 1, Enzyme Activation, External, Female, Glial Fibrillary Acidic Protein, Humans, Male, MAP Kinase Signaling System, Membrane Microdomains, Mice, Inbred C57BL, Middle Aged, Protein Transport, Receptors, sigma, RNA, Messenger, Up-Regulation |
Abstract | Cocaine abuse has been shown to accelerate the progression of human immunodeficiency virus (HIV)-1-associated neurological disorders (HANDs) partially through increasing neuroinflammatory response mediated by activated astrocytes; however, the detailed molecular mechanism of cocaine-mediated astrocyte activation is unclear. In the current study, we demonstrated increased astrogliosis in the cortical regions of brains from HIV(+) cocaine abusers compared with the HIV(+) group without cocaine abuse. We next sought to explore whether cocaine exposure could result in increased expression of glial fibrillary acidic protein (GFAP), a filament protein critical for astrocyte activation. Exposure of cocaine to astrocytes resulted in rapid translocation of sigma receptor to the plasma membrane with subsequent activation of downstream signaling pathways. Using a pharmacological approach, we provide evidence that cocaine-mediated upregulation of GFAP expression involved activation of mitogen-activated protein kinase (MAPK) signaling with subsequent downstream activation of the early growth response gene 1 (Egr-1). Egr-1 activation, in turn, caused transcriptional regulation of GFAP. Corroboration of these findings in vivo demonstrated increased expression of GFAP in the cortical region of mice treated with cocaine compared with the saline injected controls. A thorough understanding of how cocaine mediates astrogliosis could have implications for the development of therapeutic interventions aimed at HIV-infected cocaine abusers. |
DOI | 10.1007/s12035-015-9094-5 |
Alternate Journal | Mol Neurobiol |
PubMed ID | 25631712 |
PubMed Central ID | PMC4519438 |
Grant List | U24 MH100929 / MH / NIMH NIH HHS / United States R01 DA024442 / DA / NIDA NIH HHS / United States U01 MH083500 / MH / NIMH NIH HHS / United States DA020392 / DA / NIDA NIH HHS / United States R01 DA020392 / DA / NIDA NIH HHS / United States R21 DA023397 / DA / NIDA NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States R01 DA036157 / DA / NIDA NIH HHS / United States DA024442 / DA / NIDA NIH HHS / United States U01 MH083545 / MH / NIMH NIH HHS / United States P30 GM103509 / GM / NIGMS NIH HHS / United States R25 MH080661 / MH / NIMH NIH HHS / United States DA023397 / DA / NIDA NIH HHS / United States |