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    7,8-Dihydroxyflavone improves neuropathological changes in the brain of Tg26 mice, a model for HIV-associated neurocognitive disorder

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    Author
    Bryant, Joseph
    Andhavarapu, Sanketh
    Bever, Christopher
    Guda, Poornachander
    Katuri, Akhil
    Gupta, Udit
    Arvas, Muhammed
    Asemu, Girma
    Heredia, Alonso
    Gerzanich, Volodymyr
    Simard, Marc J
    Makar, Tapas Kumar
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    Date
    2021-09-16
    Journal
    Scientific Reports
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1038/s41598-021-97220-8
    https://doi.org/10.1038/s41598-021-99820-w
    Abstract
    The 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.
    Description
    The 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
    Rights/Terms
    © 2021. The Author(s).
    Keyword
    HIV-associated neurocognitive disorder (HAND)
    7,8 dihydroxyflavone
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/16690
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-021-97220-8
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