Interactive comorbidity between opioid drug abuse and HIV-1 Tat: chronic exposure augments spine loss and sublethal dendritic pathology in striatal neurons.

HIV-1 infection predisposes the central nervous system to damage by opportunistic infections and environmental insults. Such maladaptive plasticity may underlie the exaggerated comorbidity seen with HIV-1 infection and opioid abuse. Although morphine and HIV-1 Tat synergize at high concentrations to increase neuronal death in vitro, we questioned whether chronic low Tat exposure in vivo might contribute to the spectrum of neuropathology through sublethal neuronal injury.

HIV-1 Tat and morphine have interactive effects on oligodendrocyte survival and morphology.

Human immunodeficiency virus (HIV)-infected individuals who abuse opiates show faster progression to AIDS, and enhanced incidence of HIV-1 encephalitis. Most opiates with abuse liability are preferential agonists for mu-opioid receptors (MORs), and MORs are expressed on both neurons and glia, including oligodendrocytes (OLs). Tat, gp120, and other viral toxins, cause neurotoxicity in vitro and/or when injected into brain, and co-exposure to opiates can augment HIV-1 protein-induced insults to both glial and neuronal populations.

Impact of opiate-HIV-1 interactions on neurotoxic signaling.

Opiate drug abuse exacerbates the pathogenesis of human immunodeficiency virus-1 (HIV-1) in the central nervous system through direct actions on glia and neurons. Opiate abuse causes widespread disruption of astroglial and microglial function, and significant increases in astroglial-derived proinflammatory cytokines and chemokines, which likely contributes to neuronal dysfunction, death, and HIV encephalitis. Neurons are also directly affected by opiate-HIV-1 interactions.

Preferential vulnerability of astroglia and glial precursors to combined opioid and HIV-1 Tat exposure in vitro.

Human immunodeficiency virus (HIV)-1 infection can cause characteristic neural defects such as progressive motor dysfunction, striatal pathology and gliosis. Recent evidence suggests that HIV-induced pathogenesis is exacerbated by heroin abuse and that the synergistic neurotoxicity is a direct effect of heroin on the CNS, an alarming observation considering the high incidence of HIV infection with injection drug abuse. Although HIV infection results in neurodegeneration, neurons themselves are not directly infected.

Expression of TGF-beta type II receptors in the olfactory epithelium and their regulation in TGF-alpha transgenic mice.

Numerous in vitro studies of neurogenesis of olfactory receptor neurons (ORNs) suggest that transforming growth factor (TGF)-beta promotes the maturation/differentiation of olfactory progenitors. We demonstrate that in vivo both mature and immature ORNs, and possibly a basal neuronal progenitor cell, express the TGF-beta type II receptor (TGF-betaRII), suggesting that these cells are targets for TGF-beta signaling. In a previous study of neurogenesis in the OE of TGF-alpha overexpressing transgenic (T) mice, we observed an apparent reduction in the expression of olfactory marker protein (OMP), a marker of terminal differentiation in ORNs in T mice compared to nontransgenic (NT) littermate controls; this was confirmed by Western blotting and immunohistochemistry.