Swimming improves cognitive reserve in ovariectomized rats and enhances neuroprotection after global cerebral ischemia

Cognitive reserve has been proposed to account for different responses to brain damage or pathology. Factors implicated to influence cognitive reserve include cognitive engagement, physical activity, leisure activities, stress levels, and diet. Furthermore, long-term ovariectomy (OVX), such as occurs in women that have underwent surgical menopause, has been reported to increase the risk of cognitive impairment. In the current study, we examined whether swimming improves cognitive function in long-term OVX-rats. We also examined the neuroprotective effect of swimming after global cerebral ischemia (GCI) and explored the effect of swimming preconditioning on activation of the MAPK cascade signaling pathway, synaptic proteins and brain-derived growth factor (BDNF) - all factors implicated in regulating synaptic plasticity and neuroprotection in the brain. Adult Sprague-Dawley OVX-rats were randomly assigned into four groups: Sham (Sh), Sham + Swimming (Sh + Sw), Ischemia/Reperfusion (IR) and IR + Sw. Our results revealed that (1) Morris water maze and shuttle box test analysis revealed that swimming improved cognitive function in OVX-rats, (2) The levels of PSD95 and synaptophysin, as well as the protein expression of p-ERK, p-CREB and BDNF were all increased in the hippocampus after swimming with or without GCI, and (3) Swimming also increased the number of surviving neurons and IL4 protein expression, while decreasing the Iba1 (a microglia marker) level in the hippocampus. In conclusion, our study demonstrates that swimming improves memory in OVX-rats, and that swimming preconditioning enhances the neuroprotective ERK1/2/CREB/BDNF pathway signaling and ameliorates brain damage after GCI in OVX-rats, which may be closely related to induction of an IL4-mediated anti-inflammatory mechanism.