Aging modifies circadian rhythms of antioxidant enzymes and Bdnf in the temporal cortex.

DEYURKA, NICOLÁS; LACOSTE, MARÍA GABRIELA; FERRAMOLA, MARIANA LUCILA; NAVIGATORE-FONZO, LORENA; DELGADO, SILVIA MARCELA; ANZULOVICH, ANA CECILIA

Estancia Grande, San Luis

Congreso; XXXII Reunión Anual de la Sociedad de Biología de Cuyo; 2014

The brain-derived neurotrophic factor (BDNF) is a protein with a function in survival, proliferation and synaptic plasticity. It has been shown, that oxidative stress reduces Bdnf mRNA levels leading to cognitive impairments. Previously, we have shown Bdnf transcript displays a circadian rhythm in phase with the oscillation of catalase (CAT) and glutathione peroxidase (GPx) enzymes activity, in the rat hippocampus. In this study, our objectives were: to analyze the circadian variation of those antioxidant enzymes activities as well as the Bdnf mRNA levels in the rat temporal cortex and to assess the consequences of aging on those temporal patterns. Three-month-old (young) and 22-month-old (aged) Holtzman rats were maintained under 12hdark:12h-dark (constant darkness) conditions during 10 days before the experiment. Temporal cortex samples were isolated every 4 h during a 24h period and immediately frozen in liquid nitrogen. CAT and GPx enzymatic activities were determined by kinetic assays. Protein levels were measure by the Lowry method. Bdnf mRNA levels were determined by RT-PCR. For circadian analysis GraphPad Prism 5.0 and Cronos-Fit software were used. We found CAT and GPx activity fluctuates throughout a 24h period in the rat temporal cortex. CAT activity peaks at the middle of the subjective day while GPx activity is maximal around the middle of the night. Interestingly, Bdnf expression also oscillates in that brain area with its highest level occurring during the subjective day, in phase with CAT activity. Thus, we predict CAT would prevent, among others, Bdnf mRNA from oxidation, favoring the following translation. Noteworthy, aging abolished circadian rhythms of antioxidant enzymes and phase shifted circadian variation of Bdnf mRNA levels. This could be a molecular basis of altered temporal patterns of cognitive functions in aged individuals.