Electrical stimulation of cortical neurons promotes oligodendrocyte development and remyel

Electrical stimulation of cortical neurons promotes oligodendrocyte development and remyelination in

the injured spinal cord

Dan C. Li;Qun Li

【期刊名称】中国神经再生研究（英文版） 【年(卷),期】2017(012)010 【总页数】3

Background and early studies: Endogenous tri-potential neural stem cells (NSCs) exist in the adult mammalian central nervous system (CNS). In the spinal cord, NSCs distribute throughout the entire cord, but exist predominately in white matter tracts.e phenotypic fate of these cells in white matter is glial, largely oligodendrocyte, but not neuronal. Proliferating oligodendrocyte progenitor cells (OPCs) contribute to the low-rate turnover of oligodendrocytes and the maintenance of myelination of intact white matter, and possess remyelination potential in response to pathological demyelination events including spinal cord injury (SCI). Myelination in the CNS is a dynamic process that includes the

proliferation of

OPCs,

their differentiation into

mature

oligodendrocytes, and the ensheathment of axons.Endogenous, neuronal activity-dependent myelin remodeling in the adult CNS is emerging as a mechanism of CNS plasticity.The dependence of OPC proliferation on neuronal electrical activity in neighboring axons was

first demonstrated in the developing optic nerve. Unilateral sectioning of rat optic nerves just behind the eyeballs at postnatal day 8 (P8), or unilateral injection of the specific Na+ channel blocker tetrodotoxin (TTX)at P15 to eliminate the electrical activity of retinal ganglion cell axons, dramatically (86–90%) decreased the number of mitotic OPCs in the optic nerve (Barres and Raff, 1993). Meanwhile, activity-dependent oligodendrocyte development and myelination were also reported in in vitro studies. Aer an intraocular TTX injection, optic nerves were dissected from rats and cultured for several hours. A reduction in the number of cells dual-labelled with the mitotic indicator 5-bromo-2′-deoxyuridine (BrdU)and the OPC marker A2B5 was observed compared to control(Barres and Raff, 1993). In co-cultures of neurons and OPCs established from the cerebral hemispheres of 15-day-old mouse fetuses, administration of TTX significantly attenuated, while a highly selective Na+ channel activator α-ScTX enhanced, myelin formation. Consistent with these studies was our finding that decreasing neuronal activity after administration of the GABA-B receptor agonist Baclofen, which is extensively used in clinic for treatment of spasticity and reducing neuropathic pain,decreased the number of proliferating OPCs and regenerative oligodendrocytes in an animal model of SCI (Li and McDonald,unpublished).

Effect of electrical stimulation on oligodendrocyte development:

Augmentation of oligodendrocyte development and myelin remodeling by modulation of neuronal activity, which was induced through electrical stimulation, was first shown in in vitro models. In a three-compartment chamber equipped with stimulating electrodes, dorsal root ganglion (DRG) neurons and oligodendrocytes were co-cultured in side chambers,while axons growing into the central compartment beneath high-resistant barriers were electrically stimulated at 10 Hz. e electrical stimulation increased oligodendrocyte maturation and myelination through a mechanism requiring activation of sodium-dependent action potentials (Ishibashi et al., 2006).Recently, other electrical

stimulation

modalities

have

been

applied

in

neurodevelopmental studies. For instance, cultured human OPCs stimulated with a moderate intensity (0.3 T) static magnetic field (SMF) for a period of two weeks (two hours/day)displayed enhanced development

and

myelination

capacity

in

SMF-stimulated

oligodendrocytes compared to control (Prasad et al., 2017). Additionally, in vivo optogenetic activation of cortical projecting neurons in layer V promoted oligodendrogenesis and increased myelin sheath thickness in subcortical white matter tracts in mice (Gibson et al., 2014).

Functional and cognitive correlates of oligodendrocyte development: Activity-dependent oligodendrocyte development and myelination have been shown to regulate locomotive and cognitive behaviors. Selective