Evaluation of potential pro-survival pathways regulated by melatonin in a murine senescence model

Gutierrez-Cuesta, Javier; Tajes, Marta; Jimenez, Andres; Coto-Montes, Ana; Camins, Antoni; Pallas, Merce


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 beta-catenin. However, sirtuin 1 expression was significantly lower in SAMP8 than in SAMR1. In addition, acetylated p53 and NF kappa B expression were lower in SAMP8 than in SAMR1. These changes were prevented by melatonin. Moreover, the concentration/expression of alpha-secretase was lower and that of amyloid beta aggregates (A beta) was higher in untreated SAMP8 than in SAMR1. Likewise, the levels of Bid were higher, whereas Bcl-2(XL) 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.

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Título según WOS: ID WOS:000259951700017 Not found in local WOS DB
Volumen: 45
Número: 4
Editorial: Wiley
Fecha de publicación: 2008
Página de inicio: 497
Página final: 505


Notas: ISI