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dc.contributor.authorBryant, Joseph
dc.contributor.authorAndhavarapu, Sanketh
dc.contributor.authorBever, Christopher
dc.contributor.authorGuda, Poornachander
dc.contributor.authorKaturi, Akhil
dc.contributor.authorGupta, Udit
dc.contributor.authorArvas, Muhammed
dc.contributor.authorAsemu, Girma
dc.contributor.authorHeredia, Alonso
dc.contributor.authorGerzanich, Volodymyr
dc.contributor.authorSimard, Marc J
dc.contributor.authorMakar, Tapas Kumar
dc.date.accessioned2021-09-21T16:32:16Z
dc.date.available2021-09-21T16:32:16Z
dc.date.issued2021-09-16
dc.identifier.urihttp://hdl.handle.net/10713/16690
dc.descriptionThe original version of this Article contained an error in the spelling of the author J. Marc Simard which was incorrectly given as Marc J. Simard. The original Article has been corrected. 10.1038/s41598-021-99820-w
dc.description.abstractThe combined antiretroviral therapy era has significantly increased the lifespan of people with HIV (PWH), turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In PWH, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile. Therefore, we investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. In these brain regions, we observed astrogliosis, increased expression of chemokine HIV-1 coreceptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Moreover, our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB-Akt-NFkB signaling pathway in mediating these pathological hallmarks. These findings guide future research as DHF shows promise as a TrkB agonist treatment for HAND patients in adjunction to the current antiviral therapies.en_US
dc.description.urihttps://doi.org/10.1038/s41598-021-97220-8en_US
dc.description.urihttps://doi.org/10.1038/s41598-021-99820-w
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofScientific Reportsen_US
dc.rights© 2021. The Author(s).en_US
dc.subjectHIV-associated neurocognitive disorder (HAND)en_US
dc.subject7,8 dihydroxyflavoneen_US
dc.title7,8-Dihydroxyflavone improves neuropathological changes in the brain of Tg26 mice, a model for HIV-associated neurocognitive disorderen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-021-97220-8
dc.identifier.pmid34531413
dc.source.volume11
dc.source.issue1
dc.source.beginpage18519
dc.source.endpage
dc.source.countryEngland


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