Exercise enhances hippocampal‐dependent learning in the rat: Evidence for a BDNF‐related mechanism

Abstract

Short periods of forced exercise have been reported to selectively induce enhancements in hippocampal-dependent cognitive function, possibly via brain-derived neurotrophic factor (BDNF)-mediated mechanisms. In this study, we report that 1 week of treadmill running significantly enhanced both object displacement (spatial) and object substitution (nonspatial) learning. These behavioral changes were accompanied by increased expression of BDNF protein in the dentate gyrus, hippocampus, and perirhinal cortex. The effects of exercise on object substitution were mimicked by intracerebroventricular injection of BDNF protein. These data are consistent with the hypothesis that exercise has the potential to enhance cognitive function in young healthy rats, possibly via a mechanism involving increased BDNF expression in specific brain regions.

BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat

“…The results presented here demonstrate that one week of forced moderate exercise can improve spatial memory, as assessed using the object displacement task, in young, healthy adult rats, in agreement with previous findings in our laboratory [16]. Other reports in the literature suggest that in order for short-term exercise to enhance spatial learning, a deficit (insult, lesion, stress, ageing) must be present [16,[25][26][27].…”

“…We have suggested that this increase in BDNF (and the subsequent stimulation of downstream signalling pathways) is directly responsible for the improvements observed in spatial and object recognition learning, via a mechanism that is distinct from that of environmental enrichment [17]. We have also shown that the intracerebroventricular administration of a physiological dose of exogenous BDNF is sufficient to mimic the improvement in object recognition learning induced by this exercise paradigm [16]. Here, we have extended this previous work to analyse the intracellular signalling mechanisms that may underlie the observed exercise-induced and BDNF-induced cognitive improvements.…”

“…Cytochrome c was injected as it is a soluble small molecular weight protein that is inactive extracellularly [20]. The molecular weight is similar to that of BDNF, and it is often used as a control for injecting BDNF into the brain [16,21,22]. 30 min post-injection, all animals were trained in the object displacement task, and tested 24 h later.…”

“…We have shown previously that one week of forced moderate exercise can improve memory in a challenging spatial task concomitant with an increase in BDNF expression in dentate gyrus, hippocampus and perirhinal cortex [16]. We have suggested that this increase in BDNF (and the subsequent stimulation of downstream signalling pathways) is directly responsible for the improvements observed in spatial and object recognition learning, via a mechanism that is distinct from that of environmental enrichment [17].…”

The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function

“…These findings suggest that the hippocampus may have a role in this type of spatial learning. This form of learning appears to require expression of neurotrophins (Calamandrei et al, 2002;Niewiadomska et al, 2006) and exercise-induced enhancement of task performance has been associated with increases in hippocampal and perirhinal BDNF (Griffin et al, 2009). Furthermore, successful performance of the task is dependent on glutamatergic signalling through NMDA (Roullet et al, 1996;Usiello et al, 1998;Larkin et al, 2008) and AMPA receptors (Roullet et al, 2001).…”