CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates.
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.
El-Hage
Nazira
N
Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington, KY 40536, USA.
Wu
Guanghan
G
Ambati
Jayakrishna
J
Bruce-Keller
Annadora J
AJ
Knapp
Pamela E
PE
Hauser
Kurt F
KF
D015526:AIDS Dementia Complex / Q000503:physiopathology; D000818:Animals; D015696:Gene Products, tat / Q000008:administration & dosage*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015658:HIV Infections / Q000503:physiopathology; D015497:HIV-1; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000378:metabolism; D019966:Substance-Related Disorders / Q000503:physiopathology / Q000821:virology; D054322:tat Gene Products, Human Immunodeficiency Virus
C515335:Ccr2 protein, mouse; D015696:Gene Products, tat; D005904:Glial Fibrillary Acidic Protein; D009294:Narcotics; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D054322:tat Gene Products, Human Immunodeficiency Virus; D009020:Morphine