7,8-Dihydroxyflavone improves neuropathological changes in the brain of Tg26 mice, a model for HIV-associated neurocognitive disorder
Author
Bryant, JosephAndhavarapu, Sanketh
Bever, Christopher
Guda, Poornachander
Katuri, Akhil
Gupta, Udit
Arvas, Muhammed
Asemu, Girma
Heredia, Alonso
Gerzanich, Volodymyr
Simard, Marc J
Makar, Tapas Kumar
Date
2021-09-16Journal
Scientific ReportsPublisher
Springer NatureType
Article
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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-wRights/Terms
© 2021. The Author(s).Identifier to cite or link to this item
http://hdl.handle.net/10713/16690ae974a485f413a2113503eed53cd6c53
10.1038/s41598-021-97220-8
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