期刊
VIRUSES-BASEL
卷 14, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/v14061268
关键词
beta-amyloid; prepulse inhibition; RNAscope; neurodegenerative diseases; HIV-1
类别
资金
- National Institutes of Health (NIH) [MH106392, DA013137, NS100624]
- NIH through NIMH
- NINDS [U24MH100931]
- Texas NeuroAIDS Research Center (TNRC) [U24MH100930]
- Data Coordinating Center (DCC) [U24MH100925]
The prevalence of HIV-1 associated neurocognitive disorders (HAND) is higher in older individuals, and using HIV-1 Tg rats as a model, researchers found abnormal beta-amyloid accumulation in the prefrontal cortex and hippocampus, suggesting a potential mechanism underlying synaptodendritic damage in HAND.
The prevalence of HIV-1 associated neurocognitive disorders (HAND) is significantly greater in older, relative to younger, HIV-1 seropositive individuals; the neural pathogenesis of HAND in older HIV-1 seropositive individuals, however, remains elusive. To address this knowledge gap, abnormal protein aggregates (i.e., beta-amyloid) were investigated in the brains of aging (>12 months of age) HIV-1 transgenic (Tg) rats. In aging HIV-1 Tg rats, double immunohistochemistry staining revealed abnormal intraneuronal beta-amyloid accumulation in the prefrontal cortex (PFC) and hippocampus, relative to F344/N control rats. Notably, in HIV-1 Tg animals, increased beta-amyloid accumulation occurred in the absence of any genotypic changes in amyloid precursor protein (APP). Furthermore, no clear amyloid plaque deposition was observed in HIV-1 Tg animals. Critically, beta-amyloid was co-localized with neurons in the cortex and hippocampus, supporting a potential mechanism underlying synaptic dysfunction in the HIV-1 Tg rat. Consistent with these neuropathological findings, HIV-1 Tg rats exhibited prominent alterations in the progression of temporal processing relative to control animals; temporal processing relies, at least in part, on the integrity of the PFC and hippocampus. In addition, in post-mortem HIV-1 seropositive individuals with HAND, intraneuronal beta-amyloid accumulation was observed in the dorsolateral PFC and hippocampal dentate gyrus. Consistent with observations in the HIV-1 Tg rat, no amyloid plaques were found in these post-mortem HIV-1 seropositive individuals with HAND. Collectively, intraneuronal beta-amyloid aggregation observed in the PFC and hippocampus of HIV-1 Tg rats supports a potential factor underlying HIV-1 associated synaptodendritic damage. Further, the HIV-1 Tg rat provides a biological system to model HAND in older HIV-1 seropositive individuals.
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