Melatonin alters cell death processes in response to age-related oxidative stress in the brain of senescence-accelerated mice

Caballero, Beatriz; Vega-Naredo, Ignacio; Sierra, Veronica; Huidobro-Fernandez, Covadonga; Soria-Valles, Clara; De Gonzalo-Calvo, David; Tolivia, Delio; Pallas, Merce; Camins, Antonio; Rodriguez-Colunga, Maria Josefa; Coto-Montes, Ana


We studied the effect of age and melatonin on cell death processes in brain aging. Senescence-accelerated prone mice 8 (SAMP8) and senescence-accelerated resistant mice (SAMR1) at 5 and 10 months of age were used as models of the study. Melatonin (10 mg/kg) or its vehicle (ethanol at 0.066%) was administered in the drinking water from 1 to 9 months of age. Neurodegeneration, previously shown in the aged brain of SAMP8 and SAMR1 at 10 months of age, may be due to a drop in age-related proteolytic activities (cathepsin D, calpains, and caspase-3). Likewise, lack of apoptotic and macroautophagic processes were found, without apparent modification by melatonin. However, the caspase-independent cell death, owing to high p53 and apoptosis-inducing factor (AIF) levels, might be an alternative pathway of cell death in the aged brain. The main effects of melatonin treatment were observed in the aged SAMR1 mice; in this strain we observed a marked increase in antioxidant activity (catalase and superoxide dismutase). Likewise, a key antioxidant role of apoptosis-related proteins, Bcl-2 and AIF, was suggested in the aged brain of SAM mice, which was clearly influenced by melatonin. Moreover, the age-related increase of lysosomal activity of cathepsin B and a lysosomal membrane-associated protein 2 supports the possibility of the maintenance of lysosomal viability in addition to age-related impairments of the proteolytic or macroautophagic activities. The effectiveness of melatonin against the oxidative stress-related impairments and apoptosis during the aging process is, once more, corroborated in this article.

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Título según WOS: ID WOS:000261223100016 Not found in local WOS DB
Volumen: 46
Número: 1
Editorial: Wiley
Fecha de publicación: 2009
Página de inicio: 106
Página final: 114


Notas: ISI