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Review
. 2011 Jun;25 Suppl 1(Suppl 1):S61-70.
doi: 10.1016/j.bbi.2011.03.001. Epub 2011 Mar 21.

HIV-1 infection and alcohol abuse: neurocognitive impairment, mechanisms of neurodegeneration and therapeutic interventions

Yuri Persidsky  1 , Wenzhe Ho, Servio H Ramirez, Raghava Potula, Mary E Abood, Ellen Unterwald, Ronald Tuma
Affiliations
Review

HIV-1 infection and alcohol abuse: neurocognitive impairment, mechanisms of neurodegeneration and therapeutic interventions

Yuri Persidsky et al. Brain Behav Immun. 2011 Jun.

Abstract

Clinical studies indicate that alcohol dependence has an additive effect on cognitive deficits associated with HIV-1 infection. Findings in humans and animal models suggest that alcohol, similar to HIV-1, induces inflammatory processes in the brain leading to neurodegeneration. The causes of HIV-1-associated neurotoxicity are comparable to those mediating alcohol-induced neuronal injury. This review aims to present the mechanisms of the combined effects of HIV-1 and alcohol abuse in the brain and to discuss neuroprotective therapies. Oxidative stress, overproduction of pro-inflammatory factors, impairment of blood-brain barrier and glutamate associated neurotoxicity appear to play important roles in alcohol driven neurodegeneration. Diminution of neuroinflammation constitutes a logical approach for prevention of HIV-1 and alcohol mediated neurodegeneration. Agonists of cannabinoid receptor 2 (CB₂) possess potent anti-inflammatory and neuroprotective properties. We address multifaceted beneficial effects of CB₂ activation in the setting of HIV-1 brain infection and alcohol abuse.

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Figures

Figure 1
Figure 1
Up-regulation of CB2 expression in microvessels in brain tissue of alcoholics. Frontal cortex brain tissue specimens were obtained from chronic alcoholics (n=8) or aged matched controls without a history of alcohol abuse (n=6). Serial paraffin sections (5 μm thick, A-B, C-D, E-F) were cut and stained for Iba1 (monocyte-macrophage marker) and CB2. Microglial activation was found in the brain tissues of chronic alcoholics (Iba1 staining, A, C) and was accompanied by strong expression of CB2 in microvascular endothelial cells (arrowhead, B, D). Occasional perivascular macrophages and microglia without signs of activation (E) were found in control brain tissues with light CB2 staining in microvessels (F, arrowhead). Primary Abs were detected by Vectastain Elite Kit with DAB as a substrate. Stained sections were observed by light microscopy, and digital images were acquired by a cooled CCD camera. Original magnification: panels A-F × 200.
Figure 2
Figure 2
Up-regulation of CB2 expression in microvessels and macrophages/microglia in HIVE. Frontal cortex brain tissue specimens were obtained from 8 cases of HIV-1 encephalitis (HIVE) of different severity (moderate to severe(Persidsky, Ghorpade et al. 1999)) along with seronegative age-matched controls (n=4). Serial paraffin sections (5 μm thick, A-C, D-F, G-I, J-L) were cut and stained for Iba1 (macrophage marker), CB2 and HIV-1 p24. (A-C) Brain tissue from a seronegative control demonstrates the usual component of non-activated microglia (A), minimal CB2 on brain endothelium (arrowhead, B) and no p24 staining (C). (D-F) Cells of the microglial nodule are positive for Iba1 (D), CB2 (E) and p24 (F). Microvascular endothelial cells show CB2 staining (arrowhead, E). (G-I) Diffuse activation of Iba1+ microglia (G) is accompanied by CB2 expression in these cells (H) and brain endothelium (arrowhead, H). (F) Some microglia cells are p24-positive. (J-L) Perivascular macrophages (J) express CB2 (arrowhead, K) and part is HIV-1 p24+ (L). Primary Abs were detected by Vectastain Elite Kit with DAB as a substrate. Digital images were acquired by a cooled CCD camera. Original magnification: panels A-F × 200; panels G-L × 100.
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