Proenergetic effects of resveratrol in the murine neuronal cell line Neuro2a

Scope: Energy deficit is a common characteristic of neurodegenerative disorders, including Alzheimer's disease. Adenosine monophosphate activated protein kinase (AMPK) is a key enzyme maintaining energy balance by regulating the cellular uptake of glucose, β-oxidation of fatty acids, and expression of glucose transporter 4. Since resveratrol has been shown to increase the activity of AMPK, we hypothesized that it might influence energy metabolism in a model neuron-like cell line, murine Neuro2a cells. Methods and results: Resveratrol caused an elevation of adenosine triphosphate (ATP) and guanosine triphosphate (GTP) in a dose-dependent manner. The highest ATP and GTP levels achieved by treatment with resveratrol were 70.3 ± 8.2 nmol/mg protein (1.9-fold of control) and 27.2 ± 4.0 nmol/mg protein (1.7-fold of control), respectively, when cells were treated with 100 μM resveratrol for 6 h. Interestingly, increases in the total sum of all adenine nucleotides were found upon addition of resveratrol. Despite these increases in ATP, GTP, and the total adenine nucleotide pool, resveratrol treatment led to a decrease in glucose consumption and lactate release, suggesting that resveratrol does not increase energy production (e.g. via AMPK kinase activation) but rather inhibits energy-consuming processes. Conclusion: Resveratrol increases the levels of ATP and GTP, but without creating an additional glucose demand.