Molecular Neurobiology

, Volume 53, Issue 2, pp 1329–1342 | Cite as

Role of Sigma Receptor in Cocaine-Mediated Induction of Glial Fibrillary Acidic Protein: Implications for HAND

  • Lu Yang
  • Honghong Yao
  • Xufeng Chen
  • Yu Cai
  • Shannon Callen
  • Shilpa Buch
Article

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.

Keywords

Cocaine HAND Astrocyte activation σ-1R translocation Egr-1 

Notes

Acknowledgments

This work was supported by grants DA020392, DA023397, and DA024442 from the National Institutes of Health.

Conflict of Interest

The authors declare no competing financial interests.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Lu Yang
    • 1
  • Honghong Yao
    • 2
  • Xufeng Chen
    • 3
  • Yu Cai
    • 1
  • Shannon Callen
    • 1
  • Shilpa Buch
    • 1
  1. 1.Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of PharmacologyMedical School of Southeast UniversityNanjingChina
  3. 3.The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

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