Melatonin induces neural SOD2 expression independent of the NF-kappaB pathway and improves the mitochondrial population and function in old mice
Article first published online: 9 NOV 2010
© 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S
Journal of Pineal Research
Volume 50, Issue 1, pages 54–63, January 2011
How to Cite
García-Macia, M., Vega-Naredo, I., De Gonzalo-Calvo, D., Rodríguez-González, S. M., Camello, P. J., Camello-Almaraz, C., Martín-Cano, F. E., Rodríguez-Colunga, M. J., Pozo, M. J. and Coto-Montes, A. M. (2011), Melatonin induces neural SOD2 expression independent of the NF-kappaB pathway and improves the mitochondrial population and function in old mice. Journal of Pineal Research, 50: 54–63. doi: 10.1111/j.1600-079X.2010.00809.x
- Issue published online: 9 DEC 2010
- Article first published online: 9 NOV 2010
- Received June 11, 2010; accepted August 16, 2010.
- oxidative stress;
Abstract: Aging is commonly defined as a physiological phenomenon associated with morphological and functional deleterious changes in which oxidative stress has a fundamental impact; therefore, readjusting the oxidative balance should have beneficial effects. In our study, we tested the antioxidant melatonin in old mouse brains and showed positive effects at the cellular and mitochondrial levels. Melatonin attenuated β-amyloid protein expression and α-synuclein deposits in the brain compared to aged group. Furthermore, oxidative stress was increased by aging and induced the nuclear translocation of nuclear factor-kappa B (NF-κB), which was suppressed by melatonin treatment. The antioxidant mitochondrial expression, superoxide dismutase 2 (SOD2), was increased in both control and melatonin-treated old mice, despite the different activation states of the NF-κB pathway. The NF-κB pathway was activated in the old mice, which may be explained by this group’s response to the increased oxidative insult; this insult was inhibited in melatonin-treated animals, showing this group an increase in active mitochondria population that was not observed in old group. We also report that melatonin is capable of restoring the mitochondrial potential of age-damaged neurons. In conclusion, melatonin’s beneficial effects on brain aging are linked to the increase in mitochondrial membrane potential and SOD2 expression, which probably reduces the mitochondrial contribution to the oxidative stress imbalance.