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. 2010 Jul 26;479(2):128-33.
doi: 10.1016/j.neulet.2010.05.043. Epub 2010 May 21.

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

Qun Li  1 , Marcel Brus-Ramer, John H Martin, John W McDonald
Affiliations

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

Qun Li et al. Neurosci Lett. .

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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Figures

Fig 1
Fig 1
Experimental design. BDA was injected unilaterally into cortex to label the CST (green). Two weeks later, the PT electrode was implanted and stimulated daily (10 days; yellow). During the stimulation period, BrdU was administrated every other day. BrdU+ cells in dCST were counted (red).
Fig 2
Fig 2
BDA+ CST axons (green) and BrdU+ nuclei (red) in electrically stimulated animals. A: Coronal spinal cord section. More than 95% BDA labeled CST axons project in the contralateral dCST. The red box indicates the micrographs in B and E. B: T6 section. C and D: higher magnification of boxed regions in B. BrdU+ nuclei distributed predominantly in contralateral dCST and most of them apposed BDA+ axons (C; arrow). D, BrdU+ cell not contacting a BDA+ axon. E: L3 section. Parts F and G, higher magnification of boxed regions in E. Sparse BDA+ axons in the ipsilateral dCST always closely apposed BrdU+ cells (arrows). Bar, 50 μm. H: BrdU+ nuclei in the dCST of the four groups. Number of labeled cells in experimental group (contralateral dCST of stimulated animals) was significantly greater than the three control groups (two-way ANOVA; *: p< 0.0001). I: There was a significantly higher percentage of BrdU+ cells contacting BDA+ axons in the contralateral dCST than in sham animals (t-test; *: p<0.01).
Fig 3
Fig 3
Double immunolabeled BrdU+ cells and different markers in contralateral dCST in stimulated animals. A, B, C: a NG2 stained BrdU+ OPC. D, E, F: a dividing BrdU+/APC+ mature oligodendrocyte. Arrows indicate processes of NG2+ and APC+ cells apposing BDA labeled axons. G, H, I, J: A pair of BrdU and Nkx-2.2 double-labeled nuclei contacting a stimulated axon. J. Higher magnification of box in I. K, L, M: a BrdU+/GFAP+ proliferating astrocyte. N, O, P: BrdU+/Glut-1+ cell. All bars in figures, 10 μm. Q: Bar graphs showing that numbers of BrdU+/NG2+, BrdU+/APC+, and BrdU+/Nkx-2.2+ cells in the experimental group are significantly greater then control and that there is no statistical difference between experimental and control groups for BrdU+/GFAP+ and BrdU+/Glut-1+ cells (t-test; *: p < 0.05; **: p<0.01).
Fig 4
Fig 4
A BrdU+ cell in the stimulated group asymmetrically divided into two daughter cells. One cell (arrow in A) contacted labeled/stimulated dCST axons (open arrow in A) and differentiated into an NG2+ OPC (B). The sister cell, which did not contact dCST axons, did not develop this phenotype. Small open arrows in C indicate multiple appositions between stimulated axons and cell body or dendrites of the OPC. No asymmetrical divisions were found in control groups. Bar, 10 μm
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