Differential effects of wheel running and treadmill exercise on spatial memory, adult hippocampal neurogenesis and the cerebrospinal fluid proteome in rats

High levels of physical activity have been shown to induce changes in anxiety and cognitive function and to stimulate adult hippocampal neurogenesis (AHN). In rodents, wheel running and treadmill exercise paradigms are typically employed to increase physical activity to model human exercise training, but have yielded inconsistent effects on AHN and related behaviours. Thus, investigation into shared and differential molecular responses to different exercise modalities is warranted. The cerebrospinal fluid (CSF) is a proposed mediator of peripheral factors on brain plasticity and behaviours but exercise-induced changes in the CSF proteome have not yet been determined. Moreover, there is a paucity of studies directly comparing different exercise paradigms using the same durations of exercise and the same behavioural tests, on AHN and CSF proteome. This study compared the effects of eight weeks of voluntary wheel running or treadmill exercise on hippocampal-dependent behaviours, AHN and the CSF proteome in adult male Sprague-Dawley rats. While both exercise paradigms induced modest anxiolytic effects, only treadmill exercise enhanced spatial memory, a cognitive function linked to AHN. Conversely, increased AHN was observed in wheel running exercise rats only. Myelin oligodendrocyte glycoprotein and calcitonin-related polypeptide-beta were elevated in CSF by both paradigms. However, the eight-week duration of exercise may have limited the detection of molecular changes that peaked at earlier timepoints during behavioural testing. Overall, these findings demonstrate that exercise paradigms in rodents induce shared protein mediators in CSF but differentially affect hippocampal neurogenesis and suggest that exercise-induced behavioural outcomes may rely on mechanisms beyond hippocampal neurogenesis.