{"doi":"10.1002/jev2.12439","title":"Neuropathogenic role of astrocyte‐derived extracellular vesicles in HIV‐associated neurocognitive disorders","abstract":"Our previous findings demonstrated that astrocytic HIF-1α plays a major role in HIV-1 Tat-mediated amyloidosis which can lead to Alzheimer's-like pathology-a comorbidity of HIV-Associated Neurocognitive Disorders (HAND). These amyloids can be shuttled in extracellular vesicles, and we sought to assess whether HIV-1 Tat stimulated astrocyte-derived EVs (ADEVs) containing the toxic amyloids could result in neuronal injury in vitro and in vivo. We thus hypothesized that blocking HIF-1α could likely mitigate HIV-1 Tat-ADEV-mediated neuronal injury. Rat hippocampal neurons when exposed to HIV-1 Tat-ADEVs 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-1α not only reduced the biogenesis of ADEVs, as well as amyloid cargos, but also ameliorated neuronal synaptodegeneration. Next, we determined the effect of HIV-1 Tat-ADEVs carrying amyloids in the hippocampus of naive mice brains. Naive mice receiving the HIV-1 Tat-ADEVs, exhibited behavioural changes, and Alzheimer's 's-like pathology accompanied by synaptodegeneration. This impairment(s) was not observed in mice injected with HIF-1α silenced ADEVs. This is the first report demonstrating the role of amyloid-carrying ADEVs in mediating synaptodegeneration leading to behavioural changes associated with HAND and highlights the protective role of HIF-1α.","journal":"Journal of Extracellular Vesicles","year":2024,"id":424145,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1220459,"name":"Sudipta Ray","orcid":"0000-0003-3889-0136","position":1,"is_corresponding":false},{"id":1221062,"name":"Chase Ochs","orcid":null,"position":2,"is_corresponding":false},{"id":450534,"name":"Natasha Ferguson","orcid":null,"position":3,"is_corresponding":false},{"id":473072,"name":"Dinesh Y. Gawande","orcid":"0000-0001-5072-4304","position":4,"is_corresponding":false},{"id":376504,"name":"Shashank M. Dravid","orcid":"0000-0002-9912-8148","position":5,"is_corresponding":false},{"id":904273,"name":"Shannon Callen","orcid":"0000-0001-6241-3335","position":6,"is_corresponding":false},{"id":467917,"name":"Susmita Sil","orcid":"0000-0001-8941-985X","position":7,"is_corresponding":false},{"id":69462,"name":"Shilpa Buch","orcid":"0000-0002-3103-6685","position":8,"is_corresponding":false},{"id":875523,"name":"Divya T. Chemparathy","orcid":null,"position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-19T01:58:07.191194Z","pmid":"38647111","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}