Article

HIV-1 associated dementia: symptoms and causes

Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Pennsylvania 19122, USA.
Retrovirology (Impact Factor: 4.77). 02/2006; 3:28. DOI: 10.1186/1742-4690-3-28
Source: PubMed

ABSTRACT Despite the use of highly active antiretroviral therapy (HAART), neuronal cell death remains a problem that is frequently found in the brains of HIV-1-infected patients. HAART has successfully prevented many of the former end-stage complications of AIDS, however, with increased survival times, the prevalence of minor HIV-1 associated cognitive impairment appears to be rising among AIDS patients. Further, HIV-1 associated dementia (HAD) is still prevalent in treated patients as well as attenuated forms of HAD and CNS opportunistic disorders. HIV-associated cognitive impairment correlates with the increased presence in the CNS of activated, though not necessarily HIV-1-infected, microglia and CNS macrophages. This suggests that indirect mechanisms of neuronal injury and loss/death occur in HIV/AIDS as a basis for dementia since neurons are not themselves productively infected by HIV-1. In this review, we discussed the symptoms and causes leading to HAD. Outcome from this review will provide new information regarding mechanisms of neuronal loss in AIDS patients.

Download full-text

Full-text

Available from: Shohreh Amini, Jul 04, 2015
0 Followers
 · 
197 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Older human immunodeficiency virus (HIV)-1 transgenic rats are a model for HIV-1 associated neurocognitive disorders (HAND). They show behavioral changes, neuroinflammation, neuronal loss, and increased brain arachidonic acid (AA) enzymes. Aspirin (acetylsalicylate, ASA) inhibits AA oxidation by cyclooxygenase (COX)-1 and COX-2. Chronic low-dose ASA will downregulate brain AA metabolism in HIV-1 transgenic rats. Nine month-old HIV-1 transgenic and wildtype rats were given 42 days of 10mg/kg/day ASA or nothing in drinking water; eicosanoids were measured using ELISAs on microwaved brain extracts. Brain 15-epi-lipoxin A4 and 8-isoprostane concentrations were significantly higher in HIV-1 transgenic than wildtype rats; these differences were prevented by ASA. ASA reduced prostaglandin E2 and leukotriene B4 concentrations in HIV-1 Tg but not wildtype rats. Thromboxane B2, 15-HETE, lipoxin A4 and resolvin D1 concentrations were unaffected by genotype or treatment. Chronic low-dose ASA reduces AA-metabolite markers of neuroinflammation and oxidative stress in a rat model for HAND. Copyright © 2015. Published by Elsevier Ltd.
    Prostaglandins Leukotrienes and Essential Fatty Acids 01/2015; DOI:10.1016/j.plefa.2015.01.002 · 1.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: HIV-1 infection can lead to neurocognitive impairment collectively known as HIV-associated neurocognitive disorders (HAND). Although combined antiretroviral treatment (cART) has significantly ameliorated HIV's morbidity and mortality, persistent neuroinflammation and neurocognitive dysfunction continue. This review focuses on the current clinical and molecular evidence of the viral and host factors that influence glutamate-mediated neurotoxicity and neuropathogenesis as an important underlying mechanism during the course of HAND development. In addition, discusses potential pharmacological strategies targeting the glutamatergic system that may help prevent and improve neurological outcomes in HIV-1-infected subjects.
    Journal of NeuroVirology 05/2014; 20(4). DOI:10.1007/s13365-014-0258-2 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: HIV-1 Tat enables viral transcription and is also actively released by infected cells. Extracellular Tat can enter uninfected cells and affect some cellular functions. Here, we examine the effects of Tat protein on the secretory activity of neuroendocrine cells. When added to the culture medium of chromaffin and PC12 cells, Tat was actively internalized and strongly impaired exocytosis as measured by carbon fiber amperometry and growth hormone (GH) release assay. Expression of Tat mutants that do not bind to phosphatidylinositol-(4,5)-bisphophate (PI(4,5)P(2)) did not affect secretion, and overexpression of phosphatidylinositol 4 phosphate 5-kinase (PIP5K), the major PI(4,5)P(2) synthesizing enzyme, significantly rescued the Tat-induced inhibition of neurosecretion. This suggests that the inhibition of exocytosis may be the consequence of PI(4,5)P(2) sequestration. Accordingly expression of Tat in PC12 cells interfered with the secretagogue-dependent recruitment of annexin A2 to the plasma membrane, a PI(4,5)P(2)-binding protein that promotes the formation of lipid microdomains that are required for exocytosis. In addition Tat significantly prevented the reorganization of the actin cytoskeleton necessary for the movement of secretory vesicles towards plasma membrane fusion sites. Thus, the capacity of extracellular Tat to enter neuroendocrine cells and sequester plasma membrane PI(4,5)P(2) perturbs several PI(4,5)P(2)-dependent players of the exocytotic machinery, thereby affecting neurosecretion. We propose that Tat-induced inhibition of exocytosis is involved in the neuronal disorders associated with HIV-1 infection.
    Journal of Cell Science 01/2013; 126:454. DOI:10.1242/jcs.111658 · 5.33 Impact Factor