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These amyloids can be shuttled in extracellular vesicles, and we sought to assess whether HIV\u20101 Tat stimulated astrocyte\u2010derived EVs (ADEVs) containing the toxic amyloids could result in neuronal injury in vitro and in vivo. We thus hypothesized that blocking HIF\u20101\u03b1 could likely mitigate HIV\u20101 Tat\u2010ADEV\u2010mediated neuronal injury. Rat hippocampal neurons when exposed to HIV\u20101 Tat\u2010ADEVs carrying the toxic amyloids exhibited amyloid accumulation and synaptodendritic injury, leading to functional loss as evidenced by alterations in miniature excitatory post synaptic currents. The silencing of astrocytic HIF\u20101\u03b1 not only reduced the biogenesis of ADEVs, as well as amyloid cargos, but also ameliorated neuronal synaptodegeneration. Next, we determined the effect of HIV\u20101 Tat\u2010ADEVs carrying amyloids in the hippocampus of naive mice brains. Naive mice receiving the HIV\u20101 Tat\u2010ADEVs, exhibited behavioural changes, and Alzheimer's \u2019s\u2010like pathology accompanied by synaptodegeneration. This impairment(s) was not observed in mice injected with HIF\u20101\u03b1 silenced ADEVs. This is the first report demonstrating the role of amyloid\u2010carrying ADEVs in mediating synaptodegeneration leading to behavioural changes associated with HAND and highlights the protective role of HIF\u20101\u03b1.<\/jats:p>","DOI":"10.1002\/jev2.12439","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T07:34:37Z","timestamp":1713771277000},"source":"Crossref","is-referenced-by-count":26,"title":["Neuropathogenic role of astrocyte\u2010derived extracellular vesicles in HIV\u2010associated neurocognitive disorders"],"prefix":"10.1002","volume":"13","author":[{"given":"Divya T.","family":"Chemparathy","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudipta","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience 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