CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates

Received 28 December 2005; received in revised form 23 May 2006; accepted 26 May 2006. published online 11 July 2006.

Abstract

To assess the role of CCL2/MCP-1 in opiate drug abuse and HIV-1 comorbidity, the effects of systemic morphine and intrastriatal HIV-1 Tat on macrophage/microglial and astroglial activation were assessed in wild type and CCR2 null mice. Tat and/or morphine additively increased the proportion of CCL2 immunoreactive astroglia. The effects of morphine were prevented by naltrexone. Glial activation was significantly reduced in CCR2(−/−) versus wild-type mice following Tat or morphine plus Tat exposure. Thus, CCR2 contributes to local glial activation caused by Tat alone or in the presence of opiates, implicating CCR2 signaling in HIV-1 neuropathogenesis in drug abusers and non-abusers.

Abbreviations: CCL, CC or beta chemokine ligand, CCR, CC or beta chemokine receptor, GFAP, glial fibrillary acidic protein, HIV-1, human immunodeficiency virus type 1, HIVE, human immunodeficiency virus encephalitis, MCP-1 or CCL2, monocyte chemoattractant protein-1, MOR, μ-opioid receptor, RANTES or CCL5, regulated on activation normal T cell expressed and secreted, Tat, transactivator of transcription

Keywords: AIDS, Chemokines, μ-Opioid receptors, Drug abuse, Astrocytes, Microglia, CNS inflammation, Monocyte chemoattractant protein-1/CCL2

a Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington, KY 40536, USA

b Department of Ophthalmology and Visual Sciences, University of Kentucky Medical Center, Lexington, KY 40536, USA

c KY Spinal Cord and Brain Injury Research Center, University of Kentucky Medical Center, Lexington, KY 40536, USA

Corresponding author. Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536-0298, USA. Tel.: +1 859 323 6477; fax: +1 859 323 5946.

PII: S0165-5728(06)00209-8

doi:10.1016/j.jneuroim.2006.05.027

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