Endogenous rhythms of lipid peroxidation and Rc3 expression are modified in the temporal cortex of aged rats".

DEYURKA N; LORENA NAVIGATORE FONZO; CORIA-LUCERO C; LACOSTE M; ANZULOVICH A

San Miguel de Tucumán, Tucumán, Argentina.

Congreso; Tercera Reunión Conjunta de Sociedades de Biología de la República Argentina.; 2015

Asoc. de Biología de Tucumán, Soc.de Biología de Córdoba, Soc. de Biología de Cuyo y Soc. Argentina de Biología

Age-associated memory impairment has been related toincreased oxidative stress as well as to alteration of circadian rhythms in thebrain. Neurogranin (RC3), a postsynaptic protein kinase C substrate implicatedin synaptic plasticity, is expressed in different brain regions involved incognitive functions, including the temporal cortex (TC). Previously, we showedantioxidant enzymes activity and Bdnf expression follow a circadian rhythm inthe rat TC. Interestingly, aging abolished those rhythms. Continuing with thosestudies, the objectives of this work were: 1) to investigate endogenous rhythmsof lipid peroxidation, RC3 expression and the cellular clock transcriptionfactor, BMAL1, protein levels in the rat TC, and 2) to evaluate to which extentaging could affect those temporal patterns. Young (3-month old) and aged(22-month old) male Holtzman rats were maintained under constant darknessconditions during 10 days before the experiment. TC samples were isolated every4 h during a 24h period. Levels of lipid peroxidation were determined by a colorimetricassay. RC3 transcript levels were determined by RT-PCR and BMAL1 protein levelsby immunoblotting. Regulatory region of RC3 gene was scanned for clockresponsive E-box sites by using a bioinformatic tool. We found that lipoperoxidationlevels and RC3 expression oscillate on a circadian basis in the rat TC.  As expected, E-box sites were found in the RC3gene regulatory region; however, BMAL1 rhythm?s peak is in antiphase with themaximal levels of Rc3 mRNA. Consistently with what we previously observed, agingalso abolished the circadian rhythmicity of lipid peroxidation and RC3expression, probably, by flattening BMAL1 endogenous oscillation.