Opioids, Astroglial Chemokines, Microglial Reactivity, and Neuronal Injury in HIV-1 Encephalitis

Hauser, Kurt F.; El‐Hage, Nazira; Bruce‐Keller, Annadora J.; Knapp, Pamela E.

doi:10.1007/978-1-4419-0793-6_16

Cited by 1 publication

(3 citation statements)

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“…The findings indicated that opioids could accelerate and enhance the release of cytokines and chemokines caused by HIV-1 Tat [ 71 , 72 , 124 ], as well as gp120 exposure in some instances [ 86 , 181 , 272 ]. Much of this data has been reviewed previously [ 13 , 39 ].…”

Section: How Might Opiate-exposed Glia Mediate Bystander Toxicity In mentioning

confidence: 99%

“…In the present review, the term “opiate” is used to refer to alkaloids derived from the opium poppy Papaver somniferum and includes opium and heroin [ 13 ]. Opiates act by mimicking endogenous “opioid” ligands and bind “opioid” receptors [ 14 - 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…Opiates act by mimicking endogenous “opioid” ligands and bind “opioid” receptors [ 14 - 20 ]. In the case of opiate drugs with abuse liability, they principally act by triggering the μ-opioid receptor (MOR) [ 13 ], and to a lesser extent δ- (DOR) and κ- (KOR) opioid receptors. Heroin is quickly deacetylated to morphine in the CNS and morphine is the main bioactive product of heroin in the brain [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Opiate Drug Use and the Pathophysiology of NeuroAIDS

Hauser¹,

Fitting²,

Dever³

et al. 2012

CHR

109

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Opiate abuse and HIV-1 have been described as interrelated epidemics, and even in the advent of combined anti-retroviral therapy, the additional abuse of opiates appears to result in greater neurologic and cognitive deficits. The central nervous system (CNS) is particularly vulnerable to interactive opiate-HIV-1 effects, in part because of the unique responses of microglia and astroglia. Although neurons are principally responsible for behavior and cognition, HIV-1 infection and replication in the brain is largely limited to microglia, while astroglia and perhaps glial progenitors can be latently infected. Thus, neuronal dysfunction and injury result from cellular and viral toxins originating from HIV-1 infected/exposed glia. Importantly, subsets of glial cells including oligodendrocytes, as well as neurons, express µ-opioid receptors and therefore can be direct targets for heroin and morphine (the major metabolite of heroin in the CNS), which preferentially activate µ-opioid receptors. This review highlights findings that neuroAIDS is a glially driven disease, and that opiate abuse may act at multiple glial-cell types to further compromise neuron function and survival. The ongoing, reactive cross-talk between opiate drug and HIV-1 co-exposed microglia and astroglia appears to exacerbate critical proinflammatory and excitotoxic events leading to neuron dysfunction, injury, and potentially death. Opiates enhance synaptodendritic damage and a loss of synaptic connectivity, which is viewed as the substrate of cognitive deficits. We especially emphasize that opioid signaling and interactions with HIV-1 are contextual, differing among cell types, and even within subsets of the same cell type. For example, astroglia even within a single brain region are heterogeneous in their expression of µ-, δ-, and κ-opioid receptors, as well as CXCR4 and CCR5, and Toll-like receptors. Thus, defining the distinct targets engaged by opiates in each cell type, and among brain regions, is critical to an understanding of how opiate abuse exacerbates neuroAIDS.

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