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Abstract

Background: The pathogenesis of HIV-1 glycoprotein 120 (gp120) associated neuroglial toxicity remains unresolved, but oxidative injury has been widely implicated as a contributing factor. In previous studies, exposure of primary human central nervous system tissue cultures to gp120 led to a simplification of neuronal dendritic elements as well as astrocytic hypertrophy and hyperplasia; neuropathological features of HIV-1-associated dementia. Gp120 and proinflammatory cytokines upregulate inducible nitric oxide synthase (iNOS), an important source of nitric oxide (NO) and nitrosative stress. Because ascorbate scavenges reactive nitrogen and oxygen species, we studied the effect of ascorbate supplementation on iNOS expression as well as the neuronal and glial structural changes associated with gp120 exposure.

Human Immunodeficiency Virus Promotes Mitochondrial Toxicity

“…Antioxidants, including Trolox, Cu/Zn SOD1, GPx1, and PACAP27 have been found in multiple in vitro experimental approaches to reduce Tat- and gp120 induced oxidative stress and prevent neuronal apoptosis (Agrawal et al 2006; Agrawal et al 2012; Butler et al 2011; Pocernich et al 2005; Rozzi et al 2014). Ascorbate supplementation (ascorbate-2-O-phosphate) prevents the deleterious upregulation of iNOS and associated neuronal injury caused by gp120 in brain cell cultures (Walsh et al 2004). Creatine is protective against Tat-induced ATP depletion, mitochondria membrane potential reduction, ROS production, and synapse loss (Stevens et al 2014).…”

Neuronal Stress and Injury Caused by HIV-1, cART and Drug Abuse: Converging Contributions to HAND

“…However, several in vitro studies strongly suggest that CXCR4 is prominently involved in HIV-associated neuronal damage whereas CCR5 may play a dual role by being able to either serve a toxic or protective function [86,87,88,89,90,91,92]. Intact HIV-1, as well as picomolar concentrations of isolated viral envelope gp120, can induce neuronal death via CXCR4 and CCR5 receptors in neurons from humans and rodents [86,87,89,90,93,94,95,96,97,98]. …”

“…In mixed neuronal/glial cultures that recapitulate the cellular composition of the brain, HIV-1, gp120 and Tat appear to induce neuronal apoptotic death primarily in an indirect fashion via the release of toxins from macrophages/microglia [89,93,94,95,97,98,107,109,110]. Moreover, both the inactivation or depletion of macrophages and microglia basically abrogate neurotoxicity of HIV-1/gp120 in mixed neuronal/glial cultures [89,98,107,111] and it appears likely that stimulation of CXCR4 or CCR5 in macrophages/microglia is a prerequisite for the neurotoxicity of HIV-1 and gp120 [89,96,109].…”

The spreading of HIV-1 infection in the human organism is caused by fractalkine trafficking of the infected lymphocytes—a review, hypothesis and implications for treatment

“…Walsh et al [64] studied the anti-oxidant protection by ascorbate-2-O-phosphate (ASC-P) against the pathogenesis of HIV-1 gp120-associated neuroglial toxicity. Human CNS cultures were derived from 16-18-week gestation post-mortem fetal brain, and incubated with 400 lM ASC-P or vehicle for 18 h. They were then exposed to 1 nM gp120 for 24 h and the expression of inducible nitric oxide synthase (iNOS), an important source of NO, was determined.…”