Stabilization of mitochondrial function by piracetam

Piracetam is used in many countries for treatment of cognitive impairment in aging, brain injuries and dementia. The biochemical mechanism is not yet understood. We have previously shown that piracetam modifies neuronal and mitochondrial membrane properties in the aged brain. Mitochondrial failure plays a key role in Alzheimer’s disease and brain aging. Thus, we investigated the protective effects of piracetam on mitochondrial function following oxidative stress and amyloid beta treatment. Piracetam treatment at concentrations between 100 and 1000µM stabilized mitochondrial membrane potential and ATP levels in PC12 cells after oxidative stress induced by sodium nitroprusside and serum deprivation. Moreover, piracetam was able to maintain mitochondrial function after amyloid beta treatment. Brain cells of aged mice showed a decreased mitochondrial membrane potential compared to young mice. Piracetam treatment (100–500mg/kg daily) for two weeks normalized mitochondrial membrane potential in aged mice. Furthermore, piracetam treatment diminished the decrease of mitochondrial membrane potential of dissociated brain cells induced by oxidative stress and amyloid beta treatment. Aged mice had a greater benefit from piracetam treatment than young mice. Taking together, our study clearly shows stabilization of mitochondrial function as a specific and very sensitive property of piracetam, giving a plausible mechanism for the use of piracetam in brain aging and Alzheimer’s disease.

This work was supported by grants of UCB, Belgium.