<scp>HIV</scp> encephalopathy: glial activation and hippocampal neuronal apoptosis, but limited neural repair

Tauber, SC; Staszewski, Ori; Prinz, Marco; Weis, Joachim; Nolte, Kay; Bunkowski, Stephanie; Brück, Wolfgang; Nau, Roland

doi:10.1111/hiv.12288

Cited by 17 publications

(21 citation statements)

References 46 publications

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“…Consistent with our results, morphine exposure resulted in increased astrocyte activation with upregulation of GFAP expression. Similar upregulation of GFAP has also been observed in neuropathic pain [20], during morphine tolerance [21], and in HIV-1 infection of the CNS [62]. Morphine exposure of human astrocytes also increased the expression levels of proinflammatory cytokines ( TNF and IL6 ).…”

Section: Discussionsupporting

confidence: 64%

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

et al. 2018

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A recent study from our lab has revealed a link between morphine-mediated autophagy and synaptic impairment. The current study was aimed at investigating whether morphine-mediated activation of astrocytes involved the ER stress/autophagy axis. Our in vitro findings demonstrated upregulation of GFAP indicating astrocyte activation with a concomitant increase in the production of proinflammatory cytokines in morphine-exposed human astrocytes. Using both pharmacological and gene-silencing approaches, it was demonstrated that morphine-mediated defective autophagy involved upstream activation of ER stress with subsequent downstream astrocyte activation via the μ-opioid receptor (MOR). In vivo validation demonstrated preferential activation of ER stress/autophagy axis in the areas of the brain not associated with pain such as the basal ganglia, frontal cortex, occipital cortex, and the cerebellum of morphine-dependent rhesus macaques, and this correlated with increased astrocyte activation and neuroinflammation. Interventions aimed at blocking either the MOR or ER stress could thus likely be developed as promising therapeutic targets for abrogating morphine-mediated astrocytosis.

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Section: Discussionsupporting

confidence: 64%

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

et al. 2018

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“…22 Our results complement previous pathological findings that show increased level of microglial activation in HIV+ individuals. 47 Additionally, a recent positron emission tomography (PET) study also revealed similar diffuse spatial patterns of microglial activation in aviremic cognitively normal HIV+ patients compared to HIV- controls. 40 Our current results using DBSI derived metric of cellularity nicely complement the aforementioned study.…”

Section: Discussionmentioning

confidence: 90%

Diffusion Basis Spectral Imaging Detects Ongoing Brain Inflammation in Virologically Well-Controlled HIV+ Patients

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Burdo

Song

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Inflammation occurs after HIV infection and persists despite highly active antiretroviral therapy (HAART). Diffusion tensor imaging (DTI), measures HIV associated white matter changes, but can be confounded by inflammation. Currently, the influence of inflammation on white matter integrity in well-controlled HIV+ patients remains unknown. We used diffusion basis Spectrum imaging (DBSI) derived cellularity to isolate restricted water diffusion associated with inflammation separated from the anisotropic diffusion associated with axonal integrity. Ninety-two virologically suppressed HIV+ patients on HAART and 66 HIV uninfected (HIV-) controls underwent neuropsychological performance (NP) testing and neuroimaging. NP tests assessed multiple domains (memory, psychomotor speed, and executive functioning). DTI and DBSI derived fractional anisotropy (FA) maps were processed with tract based spatial statistics for comparison between both groups. Cellularity was assessed with regards to age, HIV status, and NP. Within the HIV+ cohort, cellularity was compared to clinical (HAART duration) and laboratory measures of disease (e.g. CD4 cell current and nadir). NP was similar for both groups. DTI derived FA was lower in HIV+ compared to HIV- individuals. In contrast, DBSI derived FA was similar for both groups. Instead, diffuse increases in cellularity were present in HIV+ individuals. Observed changes in cellularity were significantly associated with age, but not NP, in HIV+ individuals. A trend level association was seen between cellularity and HAART duration. Elevated inflammation, measured by cellularity, persists in virologically well-controlled HIV+ individuals. Widespread cellularity changes occur in younger HIV+ individuals and diminish with aging and duration of HAART.

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“…HIV- associated encephalitis (HIVE) was also observed in some patients at this stage. The neuropathological characteristics of HIVE include microglial nodules, multinucleated giant cells, reactive astrocytosis, microglial proliferation, myelin pallor, and infiltration of peripheral monocytes [ 28 – 31 ]. In contrast to the pre-AIDS stages, when neuronal loss is not seen, neuronal death is frequently observed in AIDS patients [ 32 ].…”

Section: Neuropathology Of Handmentioning

confidence: 99%

HIV-associated synaptic degeneration

Tang

2017

Mol Brain

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Human immunodeficiency virus (HIV) infection induces neuronal injuries, with almost 50% of infected individuals developing HIV-associated neurocognitive disorders (HAND). Although highly activate antiretroviral therapy (HAART) has significantly reduced the incidence of severe dementia, the overall prevalence of HAND remains high. Synaptic degeneration is emerging as one of the most relevant neuropathologies associate with HAND. Previous studies have reported critical roles of viral proteins and inflammatory responses in this pathogenesis. Infected cells, including macrophages, microglia and astrocytes, may release viral proteins and other neurotoxins to stimulate neurons and cause excessive calcium influx, overproduction of free radicals and disruption of neurotransmitter hemostasis. The dysregulation of neural circuits likely leads to synaptic damage and loss. Identification of the specific mechanism of the synaptic degeneration may facilitate the development of effective therapeutic approaches to treat HAND.

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HIV encephalopathy: glial activation and hippocampal neuronal apoptosis, but limited neural repair

Cited by 17 publications

References 46 publications

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

Diffusion Basis Spectral Imaging Detects Ongoing Brain Inflammation in Virologically Well-Controlled HIV+ Patients

HIV-associated synaptic degeneration

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