ENDOGENOUS RHYTHMS OF LIPID PEROXIDATION AND RC3 EXPRESSION ARE MODIFIED IN THE TEMPORAL CORTEX OF AGED RATS

DEYURKA NA; NAVIGATORE FONZO LS; CORIA LUCERO, C; LACOSTE MG; ANZULOVICH AC

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

Age-associated memory impairment has been related to increased oxidative stress as well as to alteration of circadian rhythms in the brain. Neurogranin (RC3), a postsynaptic protein kinase C substrate implicated in synaptic plasticity, is expressed in different brain regions involved in cognitive functions, including the temporal cortex (TC). Previously, we showed that antioxidant enzymes activityand Bdnf expression follow a circadian rhythm in the rat TC. Interestingly, aging abolished those rhythms. Continuing with those studies, the objectives of this work were: 1) to investigate endogenous rhythms of lipid peroxidation, RC3 expression and the cellular clock transcription factor, BMAL1, protein levels in the rat TC, and 2) to evaluate up to which extent aging could affect those temporal patterns. Young (3-month old) and aged (22-month old) male Holtzman rats were maintained under constant darkness conditions for 10 days before the experiment. TC samples were isolated every 4 h during a 24h period. Levels of lipid peroxidation were determined by a colorimetric assay. RC3 transcript levels were determined by RT-PCR and BMAL1 protein levels by immunoblotting. Regulatory region of RC3 gene was scanned for clock responsive E-box sites by using a bioinformatic tool. We found that lipoperoxidation levels and RC3 expression oscillate on a circadian basis in the rat TC. As expected, E-box sites were found in the RC3 gene regulatory region; however, BMAL1 rhythm peak is in antiphase with the maximal levels of Rc3 mRNA.Consistently with what we previously observed, aging also abolished the circadian rhythmicity of lipid peroxidation and RC3 expression, probably by flattening BMAL1 endogenous oscillation.