Temporal study of DNA methyltransferases, BDNF and TrkB in hippocampus and cerebellum during aging

ALTAMIRANO, FG; CASTRO PASCUAL, IC; CARGNELUTTI, E.; PONCE, IT; FERRAMOLA, M; LACOSTE, MG; DELGADO, MS; ANZULOVICH, AC

Congreso; 2nd Congress of the Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN); 2016

Epigenetic mechanisms, including DNA methylation whichplays a key role in memory and motor learning, are altered by aging. We aimed to evaluate the circadianvariation of DNA methyltransferases (Dnmts), Bdnf and TrkB expression in youngand aged rats. Holtzman 3- and 22-month old male rats were maintained inconstant darkness conditions during 15 days. Bdnf, TrkB, Dnmt1, Dnmt3a andDnmt3b mRNA levels were determined in hippocampus and cerebellum, isolated at4h-intervals. We previously observed that Bdnf and TrkBmRNA expression oscillated in a circadian way (p<0.05) in the young hippocampus.Aging increased Bdnf rhythm?s mesor, while abolished TrkB circadian expression. Dnmt3a mRNA expression displays acircadian rhythm (p<0,05) in young rats. The maximal expression of Dnmt3a concurswith the minimal expression of TrkB. Aging abolished Dnmt3a circadianrhythmicity in the hippocampus. We found Dnmt1 and Dnmt3b levels do notoscillate rhythmically in this brain area. In the cerebellum, TrkB and Dnmt1 mRNAlevels varied in a 24h period (p<0.05) in young rats. Aging increasedrythm?s mesor in both cases, and it also diminished TrkB rhythm?s amplitude. Inboth groups Dnmt1 maximal expression preceded TrkB minimal expression. Dnmt3aand Dnmt3b expression displayed no significant rhythm over 24 h. Alteration of Dnmts temporal patterns could be one of themolecular mechanisms of aging-associated cognitive and motor decline.