Electrical stimulation of the medullary pyramid promotes proliferation and differentiation of oligodendrocyte progenitor cells in the corticospinal tract of the adult rat

International Center for Spinal Cord Injury, Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, United States.
Neuroscience Letters (Impact Factor: 2.03). 07/2010; 479(2):128-33. DOI: 10.1016/j.neulet.2010.05.043
Source: PubMed

ABSTRACT Endogenous tri-potential neural stem cells (eNSCs) exist in the adult spinal cord and differentiate primarily into oligodendrocytes (OLs) and astrocytes. Previous in vivo and in vitro studies have shown that during development proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) depend on activity in neighboring axons. However, this activity-dependent development of OPCs has not been examined in the adult CNS. In the present study, we stimulated unilateral corticospinal (CS) axons of the adult rat and investigated proliferation and differentiation of OPCs in dorsal corticospinal tract (dCST). eNSCs were labeled with the mitotic indicator 5-bromo-2'-deoxyuridine (BrdU). Phenotypes of proliferating cells were identified by double-immunolabeling of BrdU with a panel of antibodies to cell markers: NG2, Nkx2.2, APC, GFAP, and Glut-1. Electrical stimulation of CS axons increased BrdU labeled eNSCs and promoted the proliferation and differentiation of OPCs, but not astrocytes and endothelial cells. Our findings demonstrate the importance of neural activity in regulating OPC proliferation/differentiation in the mature CNS. Selective pathway electrical stimulation could be used to promote remyelination and recovery of function in CNS injury and disease.

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Available from: John H Martin, Jan 15, 2014
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    • "Rodent studies using electrical stimulation have produced the birth of tripotential endogenous neural progenitor cells in the spinal cord [5] [57]. A large number of these cells have developed into myelin producing oligodendrocytes which provides great hope for the restoration of axonal re-myelination of damaged neurons [5] [57]. Overall, whether it be through neural or body composition alterations, regular FES activity has been shown to increase the quality of life of those with SCI [58]. "
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    ABSTRACT: This manuscript is a review of the theoretical and clinical concepts provided during an inter-institutional training program on Activity-Based Restorative Therapies (ABRT) and the perceptions of those in attendance. ABRT is a relatively recent high volume and intensity approach toward the restoration of neurological deficits and decreasing the risk of secondary conditions associated with paralysis after spinal cord injury (SCI). ABRT is guided by the principle of neuroplasticity and the belief that even those with chronic SCI can benefit from repeated activation of the spinal cord pathways located both above and below the level of injury. ABRT can be defined as repetitive-task specific training using weight-bearing and external facilitation of neuromuscular activation. The five key components of ABRT are weight-bearing activities, functional electrical stimulation, task-specific practice, massed practice and locomotor training which includes body weight supported treadmill walking and water treadmill training. The various components of ABRT have been shown to improve functional mobility, and reverse negative body composition changes after SCI leading to the reduction of cardiovascular and other metabolic disease risk factors. The consensus of those who received the ABRT training was that ABRT has much potential for enhancement of recovery of those with SCI. Although various institutions have their own strengths and challenges, each institution was able to initiate a modified ABRT program.
    Aging and Disease 08/2015; 6(4):254-61. DOI:10.14336/AD.2014.1105 · 3.07 Impact Factor
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    • "A few recent studies have attempted to obtain evidence for direct activity-dependent regulation of NG2 cell proliferation and/or differentiation under more physiological conditions . Electrical stimulation of corticospinal tracts in adult mice resulted in increased NG2 cell proliferation and oligodendrocyte differentiation (Li et al., 2010), while long-term wheel running reduced proliferation of NG2 cells and concomitantly increased oligodendrocyte differentiation in the motor cortex of adult mice (Simon et al., 2011). Whisker removal in newborn mice was reported to increase proliferation and alter the distribution of NG2 cells in one study (Mangin et al., 2012) but shown to have no effect on NG2 cell distribution in another (Hill et al., 2011) specifically in the somatosensory barrel cortex. "
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    ABSTRACT: NG2 cells (polydendrocytes) are the fourth major non-neuronal cell type in the central nervous system parenchyma. They exhibit diverse properties, ranging from their well-established role as oligodendrocyte precursors to their ability to respond to neurotransmitters released by synaptic and non-synaptic mechanisms. The functional diversity of NG2 cells has prompted the question of whether they represent a single cellular entity or multiple distinct cell populations. This review first summarizes recent findings on the nature and mechanism underlying the diversity of NG2 cells with regard to their proliferative and differentiation behavior. This will be followed by a synopsis of observations on how their microenvironment, particularly neuronal activity, influences their dynamic behavior, and how these changes in NG2 cells could in turn influence neural function and animal behavior. GLIA 2014
    Glia 08/2014; 62(8). DOI:10.1002/glia.22664 · 6.03 Impact Factor
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    • "The function of this signalling is uncertain, but in vitro neurotransmitters alter OPC migration and differentiation (Yuan et al., 1998; Gudz et al., 2006; Tong et al., 2009). Furthermore, axonal stimulation promotes OPC proliferation and OL differentiation (Li et al., 2010), whereas blocking action potentials retards myelination (Barres and Raff, 1993; Demerens et al., 1996). More recently, vesicular release of glutamate was demonstrated to promote myelin protein translation at axon-OL contacts (Wake et al., 2011), supporting the idea that synaptic communication modulates myelination. "
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    ABSTRACT: Oligodendrocyte progenitor cells (OPCs) in the postnatal mouse corpus callosum (CC) and motor cortex (Ctx) reportedly generate only oligodendrocytes (OLs), whereas those in the piriform cortex may also generate neurons. OPCs have also been subdivided based on their expression of voltage-gated ion channels, ability to respond to neuronal activity, and proliferative state. To determine whether OPCs in the piriform cortex have inherently different physiological properties from those in the CC and Ctx, we studied acute brain slices from postnatal transgenic mice in which GFP expression identifies OL lineage cells. We whole-cell patch clamped GFP-expressing (GFP(+)) cells within the CC, Ctx, and anterior piriform cortex (aPC) and used prelabeling with 5-ethynyl-2'-deoxyuridine (EdU) to assess cell proliferation. After recording, slices were immunolabeled and OPCs were defined by strong expression of NG2. NG2(+) OPCs in the white and gray matter proliferated and coexpressed PDGFRα and voltage-gated Na(+) channels (I(Na)). Approximately 70% of OPCs were capable of generating regenerative depolarizations. In addition to OLIG2(+) NG2(+) I(Na)(+) OPCs and OLIG2(+) NG2(neg) I(Na)(neg) OLs, we identified cells with low levels of NG2 limited to the soma or the base of some processes. These cells had a significantly reduced I(Na) and a reduced ability to incorporate EdU when compared with OPCs and probably correspond to early differentiating OLs. By combining EdU labeling and lineage tracing using Pdgfrα-CreER(T2) : R26R-YFP transgenic mice, we double labeled OPCs and traced their fate in the postnatal brain. These OPCs generated OLs but did not generate neurons in the aPC or elsewhere at any time that we examined.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 06/2012; 32(24):8173-85. DOI:10.1523/JNEUROSCI.0928-12.2012 · 6.34 Impact Factor
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