Can Enhancing Neuronal Activity Improve Myelin Repair in Multiple Sclerosis?

Abstract

Enhanced neuronal activity in the healthy brain can induce de novo myelination and behavioral changes. As neuronal activity can be achieved using non-invasive measures, it may be of interest to utilize the innate ability of neuronal activity to instruct myelination as a novel strategy for myelin repair in demyelinating disorders such as multiple sclerosis (MS). Preclinical studies indicate that stimulation of neuronal activity in demyelinated lesions indeed has the potential to improve remyelination and that the stimulation paradigm is an important determinant of success. However, future studies will need to reveal the most efficient stimulation protocols as well as the biological mechanisms implicated. Nonetheless, clinical studies have already explored non-invasive brain stimulation as an attractive therapeutic approach that ameliorates MS symptomatology. However, whether symptom improvement is due to improved myelin repair remains unclear. In this mini-review, we discuss the neurobiological basis and potential of enhancing neuronal activity as a novel therapeutic approach in MS.

Keywords: adaptive myelination; multiple sclerosis; neuron-oligodendroglia interactions; neuronal activation; non-invasive brain stimulation; oligodendrocyte (OL) lineage cells; remyelination.

FIGURE 1

The process of remyelination. A schematic representation of myelination in healthy condition, during demyelination and during the process of remyelination involving the migration of OPCs into the lesion from other brain regions, the proliferation of OPCs, the differentiation of new OPCs into myelinating OLs and the remyelination of naked axons by both newly differentiated OLs and pre-existing OLs. Green: neurons, light blue: OPCs, dark blue: mature OLs, purple: new-born cells.