HIV and Aging: Effects on the Central Nervous System

Cañizares, Silvia; Cherner, Mariana; Ellis, Ronald J.

doi:10.1055/s-0034-1372340

Cited by 47 publications

(34 citation statements)

References 61 publications

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“…Aging appears to be an independent risk factor in the development of neurocognitive alterations in HIV positive subjects (Canizares et al, 2014). In addition, as gp120tg animals get older, they also display more synaptic abnormalities (Toggas et al, 1994) as well as production of neurotoxic processes (Bachis et al, submitted).…”

Section: Resultsmentioning

confidence: 99%

Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala

Bachis

Forcelli

Masliah

et al. 2016

Brain, Behavior, and Immunity

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Human immunodeficiency virus type 1 (HIV) infection of the brain produces cognitive and motor disorders. In addition, HIV positive individuals exhibit behavioral alterations, such as apathy, and a decrease in spontaneity or emotional responses, typically seen in anxiety disorders. Anxiety can lead to psychological stress, which has been shown to influence HIV disease progression. These considerations underscore the importance of determining if anxiety in HIV is purely psychosocial, or if by contrast, there are the molecular cascades associated directly with HIV infection that may mediate anxiety. The present study had two goals: 1) to determine if chronic exposure to viral proteins would induce anxiety-like behavior in an animal model and 2) to determine if this exposure results in anatomical abnormalities that could explain increased anxiety. We have used gp120 transgenic mice, which display behavior and molecular deficiencies similar to HIV positive subjects with cognitive and motor impairments. In comparison to wild type mice, 6 months old gp120 transgenic mice demonstrated an anxiety like behavior measured by open field, light/dark transition task, and prepulse inhibition tests. Moreover, gp120 transgenic mice have an increased number of spines in the amygdala, as well as higher levels of brain-derived neurotrophic factor and tissue plasminogen activator when compared to age-matched wild type. Our data support the hypothesis that HIV, through gp120, may cause structural changes in the amygdala that lead to maladaptive responses to anxiety.

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Section: Resultsmentioning

confidence: 99%

Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala

Bachis

Forcelli

Masliah

et al. 2016

Brain, Behavior, and Immunity

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“…53,54 Cognitive changes related to ageing 16 might be compounded by HIV infection, 55 and low educational level 17 can contribute to poor cognitive function. Mood disorders 18 might masquerade as, or be caused by, cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

Controversies in HIV-associated neurocognitive disorders

Nightingale

Winston

Letendre

et al. 2014

The Lancet Neurology

260

197

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Cross-sectional studies show that around half of individuals infected with HIV-1 have some degree of cognitive impairment despite the use of antiretroviral drugs. However, prevalence estimates vary depending on the population and methods used to assess cognitive impairment. Whether asymptomatic patients would benefit from routine screening for cognitive difficulties is unclear and the appropriate screening method and subsequent management is the subject of debate. In some patients, HIV-1 RNA can be found at higher concentrations in CSF than in blood, which potentially results from the poor distribution of antiretroviral drugs into the CNS. However, the clinical relevance of so-called CSF viral escape is not well understood. The extent to which antiretroviral drug distribution and toxicity in the CNS affect clinical decision making is also debated.

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“…HIV-associated Neurocognitive Disorders (HAND) remain prevalent despite apparently effective suppression of HIV replication by ART in most treated individuals [1**,2**,3**]. The underlying neuropathological processes in the brain that contribute to neurological dysfunction in HAND in the era of ART are probably significantly attenuated by such therapy, resulting in a more protracted and less severe clinical course of HAND.…”

Section: Introductionmentioning

confidence: 99%

Neuropathogenesis of HIV-associated neurocognitive disorders

Chen

Gill

Kolson

2014

Current Opinion in HIV and AIDS

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Purpose of review To discuss why HIV-associated neurocognitive disorders (HAND) persist despite apparently effective HIV suppression by highly active antiretroviral therapy (ART). Recent findings As many as 50% of HIV-infected individuals suffer from HAND despite ART suppression of HIV replication to apparently undetectable levels in most treated individuals. Prior to ART, HIV-associated dementia (HAD), the severest form of HAND, affected ~20% of infected individuals; HAD now affects only ~2% of ART-treated persons, while less severe HAND forms persist. Recent studies link persistent immune activation, inflammation, and viral escape/blipping in ART-treated individuals, as well as co-morbid conditions, to HIV disease progression and increased HAND risk. Despite sustained HIV suppression in most ART-treated individuals, indicated by routine plasma monitoring and occasional CSF monitoring, ‘blips’ of HIV replication are often detected with more frequent monitoring, thus challenging the concept of viral suppression. Although the causes of HIV blipping are unclear, CSF HIV blipping associates with neuroinflammation and, possibly, CNS injury. The current theory that macrophage-tropic HIV strains within the CNS predominate in driving HAND and these associated factors is now also challenged. Summary Protection of the CNS by ART is incomplete, probably due to combined effects of incomplete HIV suppression, persistent immune activation, and host co-morbidity factors. Adjunctive therapies to ART are necessary for more effective protection.

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HIV and Aging: Effects on the Central Nervous System

Cited by 47 publications

References 61 publications

Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala

Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala

Controversies in HIV-associated neurocognitive disorders

Neuropathogenesis of HIV-associated neurocognitive disorders

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