Voluntary wheel running promotes myelination in the motor cortex through Wnt signaling in mice

Abstract

Myelin of the central nervous system exhibits strong plasticity, and skill learning exercise promotes oligodendrogenesis and adaptive myelination. Increasing evidence shows that brain structures and functions are affected by physical activity. However, the impact of voluntary physical activity on central myelination and its underlying mechanism remains unclear. The present study aimed to investigate the effect of voluntary wheel running (VWR) on central oligodendrogenesis and adaptive myelination in mice. Adult C57BL/6 J mice were placed in running wheels and allowed for voluntary running 2 weeks. Myelin levels in the central nervous system were detected using western blotting, qRT-PCR, immunohistochemical staining, and electron microscopy. Oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) were detected using immunohistochemical staining and 5-bromo-2-deoxyuridine (BrdU) assays. Motor abilities of the animals were examined using open-field, rotarod running, and beam-walking behavioral paradigms. Vital molecules of Wnt signaling were detected, and the involvement of such molecules was verified using in vitro culture of OPCs. Our results showed that VWR significantly enhanced the myelination in the motor cortex. VWR promoted the proliferation and differentiation of OPCs, and the maturation of OLs. The VWR-regulated myelination was associated with the improved motor skill and decreased mRNA level of Wnt3a/9a, whereas stimulation of Wnt signaling pathway with Wnt3a or Wnt9a suppressed OPCs proliferation and differentiation in vitro. The present study demonstrated that physical activity is highly efficient at promoting myelination in the motor cortex, by enhancing the proliferation of OPCs and accelerating the generation of myelin, providing a step forward in understanding the beneficial effects of physical activity on central myelination and its underlying mechanism.

Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes

“…Post hoc analysis revealed that the total distance traveled were not changed in the mice subjected to treadmill running (vehicle + run) compared to the control mice (vehicle + static). This is in line with the previous research (Zheng et al, 2019). Schizophrenialike model mice (MK801 + static) showed hyperlocomotion compared to the control ones (vehicle + static).…”

Evaluation of neuroprotective effects of alpha-tocopherol in cuprizone-induced demyelination model of multiple sclerosis

“…OFT and BWT were performed every 10 days for a total of 5 times (three times during weeks 1-5 and two times during weeks 6 and 7 having AT/vehicle treatment) during the experiment. BWT is a paradigm assessing sensorimotor balance and coordination ability ( 25 ).…”

Building a (w)rapport between neurons and oligodendroglia: Reciprocal interactions underlying adaptive myelination

“…For example, paradigms involving enrichment or deprivation of ll sensory or social input, such as social isolation, whisker stimulation, or monocular visual deprivation, have been shown to variously alter proliferation, differentiation, survival, and/or myelination by oligodendrocyte lineage cells (Bacmeister et al, 2020;Etxeberria et al, 2016;Fukui et al, 1991;Gyllensten and Malmfors, 1963;Hughes et al, 2018;Kato et al, 2020;Liu et al, 2012;Makinodan et al, 2012;Osanai et al, 2018;Sinclair et al, 2017;Swire et al, 2019;Tauber et al, 1980;Yang et al, 2013Yang et al, , 2020Zhao et al, 2011). The importance of experience-dependent myelination is particularly evidenced by studies showing that increased oligodendrogenesis evoked by motor, spatial, and fear-conditioning learning paradigms is necessary for proper learning and memory (McKenzie et al, 2014;Pan et al, 2020;Steadman et al, 2020;Wang et al, 2020;Xiao et al, 2016;Xin and Chan, 2020;Zheng et al, 2019;Zhou et al, 2020). Altogether, these studies convincingly demonstrate the capacity for experiential input and neuronal activity to shape oligodendroglia and myelin, but the precise cellular and molecular events underlying this plasticity are less well understood.…”