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


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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    • "Conversely, injection of alpha scorpion-toxin (a sodium channel inactivation inhibitor used to stimulate electrical activity) increased myelination (Demerens et al., 1996). Additionally, myelination of cultured dorsal root ganglia can be inhibited by administering low frequency stimulation via electrodes (Stevens et al., 1998), whereas studies using high frequency stimulation have demonstrated increases in OPC proliferation and differentiation (Li et al., 2010). Other investigations have identified potential intermediaries of neural activity (purinergic signaling) and myelination (Ishibashi et al., 2006), and OPC differentiation (Stevens et al., 2002). "
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    ABSTRACT: Many behavioral experiences are known to promote hippocampal neurogenesis. In contrast, the ability of behavioral experiences to influence the production of oligodendrocytes and myelin sheath formation remains relatively unknown. However, several recent studies indicate that voluntary exercise and environmental enrichment can positively influence both oligodendrogenesis and myelination, and that, in contrast, social isolation can negatively influence myelination. In this review we summarize studies addressing the influence of behavioral experiences on oligodendrocyte lineage cells and myelin, and highlight potential mechanisms including experience-dependent neuronal activity, metabolites, and stress effectors, as well as both local and systemic secreted factors. Although more study is required to better understand the underlying mechanisms by which behavioral experiences regulate oligodendrocyte lineage cells, this exciting and newly emerging field has already revealed that oligodendrocytes and their progenitors are highly responsive to behavioral experiences and suggest the existence of a complex network of reciprocal interactions among oligodendrocyte lineage development, behavioral experiences, and brain function. Achieving a better understanding of these relationships may have profound implications for human health, and in particular, for our understanding of changes in brain function that occur in response to experiences.
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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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    • "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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