Aging modifies the oxidative status and the circadian expression of BDNF and its TrkB receptor in the hippocampus

ALTAMIRANO, FERNANDO GABRIEL; DELLA VEDOVA, CECILIA; RINALDI TOSI, MARTÍN; DELGADO, SILVIA MARCELA; ANZULOVICH, ANA CECILIA; GÓMEZ MEJIBA, SANDRA; LACOSTE, MARÍA GABRIELA

Mar del Plata

Congreso; XXX Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Sociedad Argentina de Investigación en Neurociencias

Hippocampus plays a key role in memory and learning and is especially susceptible to oxidative stress. We previously observed BDNF and TrkB mRNA as well as antioxidant enzymes rhythms are modified in the hippocampus of aged rats. We hypothesize that aging, thorough the modification of the oxidative pattern, can alter 24h-rhythmicity. To test that, we measured the levels of BDNF and TrkB proteins, lipid peroxidation (LPO), protein carbonylation (PC) and total antioxidant capacity (TAC) throughout a 24h cycle in the hippocampus of young and aged rats. Holtzman 3- and 22-months old rats were maintained under constant darkness conditions during 15 days before the experiment. BDNF and TrkB proteins as well as TBARS (LPO), PC and TAC were determined in samples isolated at 4h-intervals. BDNF and TrkB levels varied (p˂0.05) in a 24h period, with maximal levels at circadian time (CT) 18:19±1:25 and 13:28±1:31, respectively, in young rats. Aging increased amplitude (p˂0,05) and shifted BDNF rhythm acrophase (04:45±0:50,p˂0,01); on the other hand, it abolished the TrKB oscillation. LPO, PC and TAC data didn´t fit to a cosine curve in young rats, however, we observed a significant variation between the different time points (p˂0,01). Aging abolished the LPO and TAC variation and changed PC higher concentration from CT 14 to CT 6 (p˂0,01). Alteration of oxidative status, BDNF and TrkB circadian rhythmicity could be, among others, the molecular basis of aging-associated cognitive decline.