7,8-Dihydroxyflavone improves neuropathological changes in the brain of Tg26 mice, a model for HIV-associated neurocognitive disorder.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 09 2021
16 09 2021
Historique:
received:
04
11
2020
accepted:
04
08
2021
entrez:
17
9
2021
pubmed:
18
9
2021
medline:
11
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34531413
doi: 10.1038/s41598-021-97220-8
pii: 10.1038/s41598-021-97220-8
pmc: PMC8446048
doi:
Substances chimiques
6,7-dihydroxyflavone
0
Flavones
0
Membrane Glycoproteins
0
Neuroprotective Agents
0
Ntrk2 protein, mouse
EC 2.7.10.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18519Subventions
Organisme : NINDS NIH HHS
ID : R01 NS107262
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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