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

Jian Zheng,Fei Luo,Xuan Sun,Chaolin Ma,Bao-Ming Li

doi:10.1186/s13041-019-0506-8

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.

Highlights

Myelin, the multi-laminar sheath that surrounds and insulates axons in the central nervous systems (CNS) and is formed by multipolar glial cells called oligodendrocytes (OLs), greatly facilitates the rapid transmission of neural impulses [1,2,3]
To evaluate the effect of voluntary wheel running (VWR) on myelination, we first examined the mRNA and protein levels of myelin basic protein (MBP) in three different brain regions related to motor function
Immunohistochemistry for MBP showed that VWR mice displayed a markedly enhanced myelination in the motor cortex, but not in the corpus callosum and striatum relative to controls (Fig. 1h-k)

Summary

Introduction

The multi-laminar sheath that surrounds and insulates axons in the central nervous systems (CNS) and is formed by multipolar glial cells called oligodendrocytes (OLs), greatly facilitates the rapid transmission of neural impulses [1,2,3]. In humans and non-human primates, myelination persists throughout adulthood in the CNS and involves the generation of new myelinating OLs [3, 4]. Such prolonged period of myelin development opens a window for individual experiences to influence the myelination [5, 6]. Previous studies have focused on the changes of various nerve growth factors after exercise and the effects of exercise on neurogenesis [10, 11]. Running enhances synaptic transmission and plasticity, cellular activity in the hippocampus [10, 11, 17]

Methods

Results

Conclusion