7,8-Dihydroxyflavone protects neurons against oxygen-glucose deprivation induced apoptosis and activates the TrkB/Akt pathway.

Abstract

BACKGROUND:

7,8-dihydroxyflavone (7,8-DHF), a selective agonist of tropomyosin related kinase receptor B (TrkB), is known to exert protective effects in neurodegenerative diseases. However, the role of 7,8-DHF in TrkB signaling after ischemic stroke has remained elusive.

METHODS:

In the vitro model of ischemic stroke, we investigated the neuroprotective effect of 7,8-DHF through activation of TrkB signaling. Neurons subjected to oxygen and glucose deprivation/reperfusion were treated with the protein kinase inhibitor K252a and a knockdown of TrkB. Cell counting kit-8 (CCK-8) assay, Flow Cytometric Analysis (FACS), TdT-mediated dUTP nick end labeling (TUNEL) assay were conducted for measuring cell viability and numbers of apoptotic cells. And apoptosis-associated proteins were analyzed by Western blotting.

RESULTS:

Compared with the Control group, OGD/R group revealed lower cell viability by CCK-8 assay FACS and TUNEL assay showed increased rates of neuronal apoptosis. However, 7,8-DHF treatment increased cell viability and reduced neuronal apoptosis. Western blotting indicated upregulated Bax and cleaved caspase-3 and but downregulated Bcl-2 following OGD/R. Whereas 7,8-DHF treatment downregulated Bax and cleaved caspase-3 but upregulated Bcl-2. These changes were accompanied by a significant increase in the phosphorylation of TrkB and Akt following 7,8-DHF administration. However, the administration of K252a and knockdown of TrkB could alleviate those effects.

CONCLUSION:

Our study demonstrates that activation of TrkB signaling by 7,8-DHF protects neurons against OGD/R injury via the TrkB/Akt pathway, which provides the evidence for the role of TrkB signaling in OGD-induced neuronal damage and may become a potential therapeutic target for ischemic stroke.

• Authors: Qinxiang Zhou, Hao Tang, Dingqun Bai, Yuhan Kong
• Journal: PeerJ (PeerJ) Vol. 10 Pg. e12886 ( 2022) ISSN: 2167-8359 [Print] United States
• PMID: 35186478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 Zhou et al.

Chemical References

• 6,7-dihydroxyflavone
• Proto-Oncogene Proteins c-akt
• Caspase 3
• bcl-2-Associated X Protein
• Glucose
• Oxygen
• Proto-Oncogene Proteins c-bcl-2

Topics

• Humans
• Proto-Oncogene Proteins c-akt (metabolism)
• Caspase 3 (metabolism)
• bcl-2-Associated X Protein (metabolism)
• Glucose (metabolism)
• Oxygen (metabolism)
• Apoptosis
• Neurons
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Ischemic Stroke (metabolism)