Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: Involvement of hippocampal plasticity via AKT, CREB and BDNF signaling

[Display omitted] ► Mild-intensity exercise induced muscular adaptations in aging rats. ► Mild-intensity exercise improved age-related learning and memory impairments. ► Exercise increased hippocampal plasticity via the activation of AKT, CREB and BDNF. ► Short bouts of mild exercise counteract brain function decline in aged rats. In the present study, we investigated whether mild-intensity physical exercise represents a successful strategy to enhance spatial learning and memory and hippocampal plasticity in aging rats, as previously described for long-term exposure to running wheel or treadmill exercise. Aging Wistar rats were submitted to short bouts (4–6min) of exercise treadmill during five consecutive weeks. This mild-intensity exercise program increased muscle oxygen consumption by soleus and heart in aging rats and reversed age-related long-term spatial learning and memory impairments evaluated in the water maze and step-down inhibitory avoidance tasks. Remarkably, the observed cognitive-enhancing properties of short bouts of exercise were accompanied by the activation of serine/threonine protein kinase (AKT) and cAMP response element binding (CREB) pro-survival signaling that culminates in the marked increase on the brain-derived neurotrophic factor (BDNF) mRNA expression and BDNF protein levels on the hippocampus of aging rats. Altogether, these results indicate that short bouts of exercise represent a viable behavioral strategy to improve cognition and synaptic plasticity in aging rats which should be taken into account in further studies addressing the effects of physical exercise in aging subjects.