Intraneuronal β-Amyloid Accumulation: Aging HIV-1 Human and HIV-1 Transgenic Rat Brain.
Title | Intraneuronal β-Amyloid Accumulation: Aging HIV-1 Human and HIV-1 Transgenic Rat Brain. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Li, H, McLaurin, KA, Mactutus, CF, Likins, B, Huang, W, Chang, SL, Booze, RM |
Journal | Viruses |
Volume | 14 |
Issue | 6 |
Date Published | 2022 Jun 10 |
ISSN | 1999-4915 |
Keywords | Internal |
Abstract | 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., β-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 β-amyloid accumulation in the prefrontal cortex (PFC) and hippocampus, relative to F344/N control rats. Notably, in HIV-1 Tg animals, increased β-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, β-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 β-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 β-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. |
DOI | 10.3390/v14061268 |
Alternate Journal | Viruses |
PubMed ID | 35746739 |
PubMed Central ID | PMC9230035 |
Grant List | R01 NS100624 / NS / NINDS NIH HHS / United States U24 MH100925 / MH / NIMH NIH HHS / United States U24 MH100931 / MH / NIMH NIH HHS / United States MH106392 / NH / NIH HHS / United States U24MH100930 / NH / NIH HHS / United States DA013137 / NH / NIH HHS / United States U24MH100931 / NH / NIH HHS / United States R01 MH106392 / MH / NIMH NIH HHS / United States K99 DA056288 / DA / NIDA NIH HHS / United States U24MH100925 / NH / NIH HHS / United States NS100624 / NH / NIH HHS / United States R01 DA013137 / DA / NIDA NIH HHS / United States U24 MH100930 / MH / NIMH NIH HHS / United States |