Ampelopsin attenuates brain aging of D-gal-induced rats through miR-34a-mediated SIRT1/mTOR signal pathway

Area of Science:

• Neuroscience
• Molecular Biology
• Pharmacology

Background:

• Aging-related neurodegenerative diseases, like Alzheimer's disease, have complex molecular mechanisms.
• MicroRNAs (miRNAs), particularly miR-34a, are implicated in aging and associated diseases, making miR-34a a potential therapeutic target.
• Ampelopsin (dihydromyricetin, DHM), a natural flavonoid, exhibits anti-inflammatory, anti-oxidative, and anti-cancer properties and shows promise as an anti-aging compound for neurodegenerative diseases.

Purpose of the Study:

• To investigate the effect of DHM on D-galactose (D-gal)-induced brain aging in a rat model.
• To explore the role of miR-34a in D-gal-induced brain aging and its modulation by DHM.
• To elucidate the molecular pathways, including SIRT1 and mTOR, involved in DHM's neuroprotective effects.

Main Methods:

• Induction of brain aging in rats using D-galactose.
• Treatment of rats with DHM.
• Quantification of miR-34a expression.
• Analysis of apoptosis and autophagy in hippocampal neurons.
• Investigation of SIRT1 and mTOR signaling pathways.

Main Results:

• D-galactose administration led to increased miR-34a expression in the aging rat brain.
• DHM treatment significantly suppressed miR-34a expression.
• DHM inhibited D-gal-induced neuronal apoptosis and improved impaired autophagy in the hippocampus.
• DHM activated autophagy by up-regulating SIRT1 and down-regulating mTOR, mediated by the suppression of miR-34a.

Conclusions:

• DHM demonstrates potential in preventing and treating D-galactose-induced brain aging.
• The protective effects of DHM are mediated through the miR-34a-SIRT1-mTOR signaling pathway.
• DHM's ability to modulate miR-34a and influence autophagy and apoptosis highlights its therapeutic potential for aging-related neurodegeneration.