Contribution of CNS cells in NeuroAIDS

Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector -125, Noida (UP) - 201 303, India.
Journal of pharmacy & bioallied sciences 10/2010; 2(4):300-6. DOI: 10.4103/0975-7406.72129
Source: PubMed


NeuroAIDS is becoming a major health problem among AIDS patients and long-term HIV survivors. As per 2009 estimates of UNAIDS report, more than 34 million people have been infected with HIV out of which ≥ 50% show signs and symptoms of neuropsychiatric disorders. These disorders affect central nervous system (CNS) and peripheral nervous systems (PNS). CNS is one of the most protected organ systems in body which is protected by blood-brain barrier (BBB). Not only this, most of the cells of CNS are negative for receptors and co-receptors for HIV infections. Neurons have been found to be completely nonpermissive for HIV infection. These facts suggest that neurotoxicity could be an indirect mechanism responsible for neuropsychiatric complications. In this review, we will discuss the importance of different cell types of CNS and their contribution toward neurotoxicity.

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    • "most severe condition of HIV - associated dementia ( HAD ; Antinori et al . , 2007 ; Woods et al. , 2009 ) , manifested pathologically as HIV encephalitis ( HIVE ; Zink et al . , 1999 ) , through interactive cellular events ( Kaul et al . , 2005 ) . As neurons have not generally been found to be infected by HIV ( Kramer - Hammerle et al . , 2005 ; Verma et al . , 2010 ) , most of the HIV - associated neurotoxicity can occur from bystander effects through the actions of infected / activated glia ( Kaul et al . , 2001 ) . Microglia are the primary target of HIV in the brain ( Kramer - Hammerle et al . , 2005 ) , and this cell type can release various toxic and inflammatory factors during the course of "
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    ABSTRACT: We investigated the role of autophagy in HIV-infected subjects with neurocognitive impairment (NCI) ± HIV encephalitis (HIVE), many of which had a history of polysubstance abuse/dependence, using post-mortem brain tissues to determine whether differences in autophagy related factors may be more associated with NCI or NCI-encephalitis. Using qRT-PCR, we detected significant differences in gene expression levels with SQSTM1, LAMP1 higher in HIV-infected subjects without NCI while ATG5, SQSTM1 were then lower in HIV infection/NCI and ATG7, SQSTM1 being higher in NCI-HIVE. Immunohistochemical labeling of these autophagy associated proteins (also including Beclin 1 and LC3B) in Iba1-positive microglial cells showed generally higher immunoreactivity in the NCI and NCI-HIVE groups with more focal vs. diffuse patterns of expression in the NCI-HIVE group. Furthermore, analysis of microarray data from these same subjects found significantly higher levels of LAMP1 in NCI-HIVE compared to uninfected subjects in the basal ganglia. Finally, we tested the effect of supernatant from HIV-1-infected microglia and HIV-1 Tat protein in combination with morphine on neurons in vitro and found opposing events with both significant inhibition of autophagic flux and reduced dendrite length for morphine and supernatant treatment while Tat and morphine exposure resulted in lower autophagic activity at an earlier time point and higher levels in the later. These results suggest autophagy genes and their corresponding proteins may be differentially regulated at the transcriptional, translational, and post-translational levels in the brain during various stages of the HIV disease and that infected individuals exposed to morphine can experience mixed signaling of autophagic activity which could lead to more severe NCI than those without opioid use.
    Full-text · Article · Jul 2015 · Frontiers in Microbiology
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    • "Such infection is restricted at both virus entry and post-entry viral gene expression [17]. It has been shown that in HIV-1 infected individuals astrocytosis can be triggered not only by virus infection [18], but also induced by viral proteins or other macrophage products [19]. HIV-1 Tat-mediated brain lesions have also been reported to be associated with an increase of astrocytosis. "
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    ABSTRACT: Astrocytes play an important role in maintaining an optically suited milieu for neuronal functionality, and are involved in the progression and outcome of many neuropathological conditions. It becomes increasingly evident that astrocytes are significant contributors to HIV-1 associated neurological disorders by modulating the microenvironment in the central nervous system and releasing proinflammatory cytokines. Recent studies have revealed direct metabolic interactions between neurons and astrocytes observed particularly in HIV-1-associated neurological disorders by which astrocytic dysfunctions disregulate extracellular K+ homeostasis, intracellular calcium concentration, glutamate clearance, and blood brain barrier integrity and permeability. Such dysfunctions are amplified via gap junctions, directly or indirectly impacting surrounding neurons and significantly contributing to the pathogenesis of HIV-1-associated neuropathology. In this review, we tentatively address recent progresses on the roles astrocytes may play in HIV-1-associated neurotoxicity.
    Full-text · Article · Nov 2013 · Journal of AIDS & Clinical Research
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    • "or 5) Is it a combined effect of all these possibilities? The present understanding of NeuroAIDS and its causes remain still unclear [8]. "
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    ABSTRACT: Improved antiretroviral treatments are still unable to cure HIV infections, therefore chronically lowlevels of HIV replication continues in patients. Long-term low replication of HIV leads toaccumulation of virotoxins, which could be a reason for neurotoxicity in long-term HIV survivors.Nowadays, more than 50% of HIV patients are presented with neuropsychiatric complications,known as NeuroAIDS. Increase in life-span of HIV seropositives, along with addition of newinfections every year is a real concern for NeuroAIDS as a new and emerging health problem.
    Preview · Article · Nov 2010 · IIOAB Journal
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