Effect of aging on brain-derived neurotrophic factor, proBDNF, and their receptors in the hippocampus of Lou/C rats

Abstract

The interest in understanding healthy aging has prompted scientist to look for animal models presenting this feature. Lou/C rats, an inbred strain of Wistar origin, is an animal model of successful aging with a longer lifespan and preserved memory capacities than most laboratory rat strains. In an attempt to shed light on this remarkable aging feature, we investigated the hippocampal patterns (mRNA and proteins) of some protective and plasticity-related molecules, i.e., brain-derived neurotrophic factor (BDNF), its precursor proBDNF, and its receptors (i.e., TrkB.FL, TrkB.T1, TrkB.T2, and p75). Using different experimental approaches, we compared these characteristics in young and aged Lou/C versus matched Wistar rats (the most appropriate controls). Data showed that young and aged Lou/C rats had higher amounts of BDNF and proBDNF content than Wistar rats. In contrast, proBDNF content was reduced in aged Lou/C rats and increased in aged Wistar rats. With aging, Lou/C rats showed a weaker decrease in TrkB.FL receptors than Wistar rats and no changes in TrkB.T1 receptors, which, contrarily, were increased in aged Wistar rats. Overall, these observations could account for the preserved cognitive performances and memory-dependent mechanisms, such as the unaltered long-term potentiation (LTP), throughout the lifespan recently reported in the Lou/C strain. Data suggest that boosting the expression or activity of these endogenous protective systems may be a promising alternative for combating some age-related cognitive declines. Therefore, Lou/C rats represent an interesting model of healthy aging for studying plasticity-related processes that evolve from youthfulness to aging.