HIV-1 Infection and its Impact on the HPA Axis, Cytokines, and Cognition

Kumar, Mahendra; Kumar, Adarsh; Waldrop, Drenna; Antoni, Mike; Eisdorfer, Carl

doi:10.1080/10253890310001605376

Cited by 35 publications

(29 citation statements)

References 41 publications

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“…Previous investigations have demonstrated cause and effect relationships between production of HIV-1 proteins gp120 and Tat, and neuronal damage [17,19,21]. Consistent with these findings clinical reports detail correlations between HIV-1 proteins, IFN-γ, and neuron cell loss resulting in cognitive decline in HAD patients [14,19,23].…”

Section: Discussionsupporting

confidence: 72%

“…Later in the symptomatic phase of HAD, usually coinciding with CD4+ T-cell depletion to levels lower than 200 cells/mm 3 , the virus is sustained in the CNS primarily by resident microglia and macrophages that have invaded from peripheral tissues. These cells seemingly serve as both viral factories and as mediators for inflammatory events resulting in neuropathology and subsequent neuropsychiatric impairment; the sequelae of HAD linked to "AIDS dementia-associated neuron damage" [1,14,23,31]. Indeed, pathologic CNS immune dysfunction has been widely explored in many past studies of microglia; the primary host cells for HIV-1 in the CNS [8,13,32,33].…”

Section: Introductionmentioning

confidence: 99%

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EGCG mitigates neurotoxicity mediated by HIV-1 proteins gp120 and Tat in the presence of IFN-γ: Role of JAK/STAT1 signaling and implications for HIV-associated dementia

et al. 2006

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Human immunodeficiency virus (HIV)-1 infection of the central nervous system occurs in the vast majority of HIV infected patients. HIV-associated dementia (HAD) represents the most severe form of HIV-related neuropsychiatric impairment and is associated with neuropathology involving HIV proteins and activation of proinflammatory cytokine circuits. Interferon-γ (IFN-γ) activates the JAK/STAT1 pathway, a key regulator of inflammatory and apoptotic signaling, and is elevated in brains of HIV-1 infected brains progressing to HAD. Recent reports suggest that green tea derived (-)-epigallocatechin-3-gallate (EGCG) can attenuate neuronal damage mediated by this pathway in conditions such as brain ischemia. In order to investigate the therapeutic potential of EGCG to mitigate the neuronal damage characteristic of HAD, IFN-γ was evaluated for its ability to enhance well-known neurotoxic properties of HIV-1 proteins gp120 and Tat in primary neurons and mice. Indeed, IFN-γ enhanced the neurotoxicity of gp120 and Tat via increased JAK/STAT signaling. Additionally, primary neurons pretreated with a JAK1 inhibitor or those derived from STAT1-deficient mice were largely resistant to the IFN-γ enhanced neurotoxicity of gp120 and Tat. Moreover, EGCG treatment of primary neurons from normal mice reduced IFN-γ enhanced neurotoxicity of gp120 and Tat, while attenuating JAK/STAT1 pathway activation. EGCG was also found to attenuate the neurotoxic properties of HIV-1 proteins in the presence of IFN-γ in vivo. Taken together, these data suggest that EGCG attenuates the neurotoxicity of IFN-γ augmented neuronal damage from HIV-1 gp120 and Tat both in vitro and in vivo. Thus EGCG ‡

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

EGCG mitigates neurotoxicity mediated by HIV-1 proteins gp120 and Tat in the presence of IFN-γ: Role of JAK/STAT1 signaling and implications for HIV-associated dementia

et al. 2006

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“…Moreover, on the basis of various reports, we proposed that changes in HPA axis activity may be a consequence of molecular mimicry between the HIV-1 genome and key control elements of the HPA axis [1] . For instance, it has been reported that the corticotrophin releasing hormone (CRH) response element binding protein (REB) binds to a specific region of the POMC promoter with sequence CTGTGCGCGCAG.…”

Section: Introductionmentioning

confidence: 99%

Cortisol Response Mediates HIV-1-Related Cognitive Deficits Among Injecting Drug Abusers

Ownby¹,

Waldrop-Va²,

Kumar³

et al. 2006

American J. of Infectious Diseases

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Abstract:The cortisol response is an important measure of the endocrine activity to environmental challenges and has been related to cognitive function and mood. Previous studies have shown that the cortisol response to stress is dysregulated in persons with HIV-1 infection. Since cortisol is neurotoxic and its levels have been related to cognitive dysfunction in various disorders, it is possible that neuroendocrine dysregulation may also be related to cognitive dysfunction in individuals with HIV-1 infection. The purpose of this study was to test the hypothesis that the cortisol response to an alpha adrenergic challenge, cold pressor, is related to cognitive function in HIV-infected injecting drug abusers. We used growth curve modeling to study the relationship of cold pressor challenge stimulated cortisol response to scores on the modified HIV Dementia Scale (mHDS). To test this hypothesis, we assessed the effects of HIV-1 infection on the HDS score directly and indirectly via pattern of cortisol response. The analysis showed that HIV-1 infection was directly related to mHDS performance and that it also influenced scores on the mHDS by way of individuals' pattern of cortisol response. Cortisol response to -adrenergic challenge thus may mediate cognitive deficits in individuals with HIV-1 infection. These findings further emphasize the importance of understanding the role of stress in the cognitive problems associated with HIV-1 infection.

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“…Additionally, recent reports suggest that changes in HPA axis regulation may be a consequence of molecular mimicry in the HIV virus genome and the key control elements of the HPA axis [12,13] . For instance, viral proteins gag and Ltr regions may interact with the pro-opiomelanocortin (POMC) promoter normally regulated by corticotrophin releasing hormone (CRH) [14,15] .…”

Section: Introductionmentioning

confidence: 99%

Neuroendocrine Abnormalities in Drug Abusers and HIV-Infected Individuals: Cortisol Response to Cold Pressor Challenge

Kumar¹,

Waldrop-Va²,

Kumar³

2006

American J. of Infectious Diseases

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Although endocrine abnormalities have been reported in HIV-1 infection, the role of risk factors is not understood. Injecting drug use (IDU) is an important risk factor for contracting HIVinfection and studies suggest that substance use may also be associated with endocrine dysfunction. In order to investigate hypothalamic pituitary adrenal (HPA) axis activity in this population, this study investigated cortisol response to the cold pressor challenge in IDUs with and without HIV infection. After controlling for the effects of gender, duration of marijuana use and time since the last use of heroin, the findings show that the pattern of cortisol response depended upon HIV serostatus. Cortisol levels peaked later in HIV+ IDUs and recovered at a slower rate than HIV negative IDUs. These findings support our hypothesis that dysregulation in HPA axis activity occurs in HIV infected IDUs.

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HIV-1 Infection and its Impact on the HPA Axis, Cytokines, and Cognition

Cited by 35 publications

References 41 publications

EGCG mitigates neurotoxicity mediated by HIV-1 proteins gp120 and Tat in the presence of IFN-γ: Role of JAK/STAT1 signaling and implications for HIV-associated dementia

EGCG mitigates neurotoxicity mediated by HIV-1 proteins gp120 and Tat in the presence of IFN-γ: Role of JAK/STAT1 signaling and implications for HIV-associated dementia

Cortisol Response Mediates HIV-1-Related Cognitive Deficits Among Injecting Drug Abusers

Neuroendocrine Abnormalities in Drug Abusers and HIV-Infected Individuals: Cortisol Response to Cold Pressor Challenge

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