Evaluation of potential pro-survival pathways regulated by melatonin in a murine senescence model
Article first published online: 13 AUG 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard
Journal of Pineal Research
Volume 45, Issue 4, pages 497–505, November 2008
How to Cite
Gutierrez-Cuesta, J., Tajes, M., Jiménez, A., Coto-Montes, A., Camins, A. and Pallàs, M. (2008), Evaluation of potential pro-survival pathways regulated by melatonin in a murine senescence model. Journal of Pineal Research, 45: 497–505. doi: 10.1111/j.1600-079X.2008.00626.x
- Issue published online: 9 OCT 2008
- Article first published online: 13 AUG 2008
- Received May 22, 2008; accepted July 11, 2008.
- amyloid β;
- cysteine proteases;
Abstract: We examined the effect of melatonin on pro-survival processes in three groups of mice. Untreated senescence-accelerated mice (SAMP8), melatonin-treated SAMP8 and untreated senescence-accelerated resistant mice (SAMR1) of 10 months old were studied. Melatonin (10 mg/kg) or vehicle (ethanol at 0.066%) was supplied in the drinking water from the end of the first month until the end of the ninth month of life. Differences in the Akt/Erk1-2 pathway and downstream targets were examined and no significant changes were observed, except for β-catenin. However, sirtuin 1 expression was significantly lower in SAMP8 than in SAMR1. In addition, acetylated p53 and NFκB expression were lower in SAMP8 than in SAMR1. These changes were prevented by melatonin. Moreover, the concentration/expression of α-secretase was lower and that of amyloid β aggregates (Aβ) was higher in untreated SAMP8 than in SAMR1. Likewise, the levels of Bid were higher, whereas Bcl-2XL levels were lower in SAMP8 than in SAMR1. Melatonin reduced all these changes. We conclude that melatonin improves pro-survival signals and reduces pro-death signals in age-related impairments of neural processes.