Key Points
- Brain damage lowered signals needed for healthy brain function
- Exercise increased genes involved in brain repair and plasticity
- Resveratrol and fisetin also improved these signals
- Combination exercise, resveratrol, and fisetin produced the strongest results
- The combined treatment increased BDNF nearly fivefold
Methods
The researchers created Alzheimerโs-like changes by injecting amyloid-beta directly into a brain area important for learning and memory.
Mice were divided into five groups:
- Control: No AD received or intervention
- AD: Mice received amyloid-beta injections only
- AD + AT: Mice received amyloid-beta injections and underwent aerobic training (AT)
- AD + RSV + Fis: Mice received amyloid-beta injections and 25 mg/kg resveratrol (RSV) and 20 mg/kg fisetin (Fis) orally
- AD + AT + RSV + Fis: Mice received amyloid-beta injections, aerobic training, and 25 mg/kg RSV and 20 mg/kg Fis orally.
The exercise program lasted eight weeks and was performed on a treadmill five days per week. By the end of the program, the mice exercised for 60 minutes per session.
Exercise or Supplements Alone Improved Brain-Supporting Signals
Alzheimerโs disease is associated with the gradual loss and dysfunction of neurons, which can impair memory and thinking over time.
In this study, amyloid-beta exposure sharply reduced the activity of BDNF, VEGF, and FGF7. These genes are involved in neuroplasticity, blood-vessel support, and communication between brain cells.
Mice that received resveratrol and fisetin had significantly higher expression of all three genes than untreated Alzheimerโs mice.
โThe expression of the BDNF/VEGF/FGF gene in AD + RSV + Fis had a significant increase in comparison to AD.โ
Aerobic exercise produced an even greater increase in several of these signals.
โThere was a significant increase in the expression of the BDNF/VEGF/FGF gene in AD + AT compared to AD + RSV + Fis.โ
All treated groups showed higher gene expression than untreated Alzheimerโs mice, suggesting that both exercise and supplementation influenced pathways involved in brain maintenance and repair.
All treated groups saw an increase in gene regulation, suggesting the benefits of exercise or supplementation for Alzheimerโs
Combined Treatment Produced the Strongest Increase
Among the Alzheimerโs groups, mice receiving aerobic training, resveratrol, and fisetin had the highest expression of BDNF, VEGF, and FGF7.
Compared with untreated Alzheimerโs mice, the combined intervention increased:
- BDNF by approximately 4.9 times
- VEGF by approximately 3.5 times
- FGF7 by approximately 2.5 times
โFurther, the expression of the BDNF/ VEGF/FGF gene in AD + AT + + RSV + Fis had a significant increase compared to AD + AT.โ
The figure shows that Alzheimerโs mice receiving both aerobic training and resveratrol-fisetin had the highest BDNF expression among the treated Alzheimerโs groups. BDNF levels remained below those seen in healthy control mice.
The researchers described the combined response as synergistic:
โA synergistic and significant effect of AT, RSV, and Fis compounds on gene expression and behavioral patterns was observed in the RSV-Fis + AT + AD group compared to other groups.โ
Conclusion
The results suggest that resveratrol and fisetin, particularly when combined with aerobic exercise, may help restore brain-supporting signaling that is reduced by Alzheimerโs-like damage.
The combined intervention produced the greatest increase in BDNF, VEGF, and FGF7 gene expression. These factors work together to support neuron survival, blood-vessel health, synaptic communication, and the brainโs ability to adapt.
โThe use of RSV and Fis, along with ATโฆis effective in controlling brain damage and ultimately leads to the improvement of AD.โ
Combining movement with resveratrol and fisetin offer promising therapeutic potential against cognitive decline associated with Alzheimerโs disease.
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