| dcterms.abstract | Aerobic exercise is known to influence adult hippocampal neurogenesis, but exercise’s ability to modulate oligodendroglia has been largely speculated upon based on MRI findings in human studies. Yet recent work indicates that adult oligodendroglia can be highly responsive to physical activities such as motor learning. However, several outstanding questions remain, including: does exercise affect oligodendroglia or myelination in juveniles, and, does exercise affect oligodendroglia or myelination in demyelinating conditions? To address this, juvenile and adult mice were provided with free access to a running wheel for four weeks followed by analyses of oligodendrocyte development and myelination in the prefrontal cortex, a late myelinating area involved in working memory, and the corpus callosum, a white matter tract with often reported oligodendroglial-responses to physical activity related paradigms. An effect of exercise on working memory (trending) and prefrontal cortex oligodendrocyte development was noted in juvenile mice, yet surprisingly exercise-mediated oligodendroglia effects were distinct depending on the age of the mouse. In the prefrontal cortex, oligodendrocyte progenitor proliferation increased in exercising juveniles compared to sedentary aged-matched control mice, whereas exercise did not increase proliferation in the prefrontal cortex of adult mice. Inversely, the production of newly-born oligodendrocytes was increased by exercise in adult, but not juvenile, mice. Although there were no overall changes in levels of myelin gene transcripts, the levels of Monocarboxylate Transporter 1 transcripts were elevated in the exercising adult prefrontal cortex. Monocarboxylate Transporter 1 is a lactate transporter enriched in oligodendroglia that is important for oligodendrocyte metabolism during active myelination and for oligodendroglial metabolic support of axons, indicating that exercise may act to improve oligodendroglial metabolic functions. To induce demyelinating conditions, we administered cuprizone for 4.5 weeks, a toxic demyelinating agent to adult mice, and ascertained that cuprizone-treated mice ran extensively, decreasing their daily distance levels only slightly at the height of disability. We then assessed oligodendroglial dynamics, a period at which significant demyelination has occurred but limited remyelination has begun. Specifically, in commonly affected posterior corpus callosum areas in cuprizone treated exercising mice, we noted reductions in: oligodendrocyte cell death, pathological increases of OPC and Microglial densities, as well as OPC proliferation. This exercise may help to ameliorate some of the hallmarks of demyelination. Overall, our findings reveal exercise may exert pronounced effects during juvenile prefrontal cortex oligodendrocyte development, with differential effects at other times and regions, providing new insights into cellular responses that may differentially underlie cognitive benefits to teenagers and adults in response to exercise. | |
