Cholinergic enhancement of cell proliferation in the postnatal neurogenic niche of the mammalian

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Deuchars, SA ; Corns, LF ; Atkinson, L ; Daniel, J ; Edwards, IJ ; New, L ; Deuchars, J (2015)
  • Publisher: Wiley

The region surrounding the central canal (CC) of the spinal cord is a highly plastic area, defined as a postnatal neurogenic niche. Within this region are ependymal cells which can proliferate and differentiate to form new astrocytes and oligodendrocytes following injury and cerebrospinal fluid contacting cells (CSFcCs). The specific environmental conditions, including the modulation by neurotransmitters that influence these cells and their ability to proliferate, are unknown. Here we show that acetylcholine promotes the proliferation of ependymal cells in mice under both in vitro and in vivo conditions. Using whole cell patch clamp in acute spinal cord slices, acetylcholine directly depolarised ependymal cells and CSFcCs. Antagonism by specific nicotinic acetylcholine receptor (nAChR) antagonists or potentiation by the α7*nAChR modulator PNU 120596 revealed that both α7*nAChRs and non-α7*nAChRs mediated the cholinergic responses. Using the nucleoside analogue EdU (5-ethynyl-2'-deoxyuridine) as a marker of cell proliferation, application of α7*nAChR modulators in spinal cord cultures or in vivo induced proliferation in the CC region, producing Sox-2 expressing ependymal cells. Proliferation also increased in the white and grey matter. PNU 120596 administration also increased the proportion of cells co-expressing oligodendrocyte markers. Thus, variation in the availability of acetylcholine can modulate the rate of proliferation of cells in the ependymal cell layer and white 1 and grey matter through α7*nAChRs. This study highlights the need for further investigation into how neurotransmitters regulate the response of the spinal cord to injury or during aging.
  • References (44)
    44 references, page 1 of 5

    1 Pfenninger CV, Steinhoff C, Hertwig F et al. Prospectively isolated CD133/CD24- positive ependymal cells from the adult spinal cord and lateral ventricle wall differ in their long-term in vitro self-renewal and in vivo gene expression. Glia 2011;59:68-81.

    2 Johansson CB, Momma S, Clarke DL et al. Identification of a neural stem cell in the adult mammalian central nervous system. Cell 1999;96:25-34.

    3 Mothe AJ, Tator CH. Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat. Neuroscience 2005;131:177-187.

    4 Meletis K, Barnabe-Heider F, Carlen M et al. Spinal cord injury reveals multilineage differentiation of ependymal cells. Plos Biol 2008;6:1494-1507.

    5 Barnabe-Heider F, Goritz C, Sabelstrom H et al. Origin of new glial cells in intact and injured adult spinal cord. Cell Stem Cell 2010;7:470-482.

    6 Danilov AI, Covacu R, Moe MC et al. Neurogenesis in the adult spinal cord in an experimental model of multiple sclerosis. Eur J Neurosci 2006;23:394-400.

    7 Marichal N, Garcia G, Radmilovich M et al. Enigmatic central canal contacting cells: Immature Neurons in "standby mode"? J Neurosci 2009;29:10010-10024.

    8 Stoeckel ME, Uhl-Bronner S, Hugel S et al. Cerebrospinal fluid-contacting neurons in the rat spinal cord, a gamma-aminobutyric acidergic system expressing the P2X(2) subunit of purinergic receptors, PSA-NCAM, and GAP-43 immunoreactivities: Light and electron microscopic study. J Compar Neurol 2003;457:159-174.

    9 Reimer MM, Norris A, Ohnmacht J et al. Dopamine from the brain promotes spinal motor neuron generation during development and adult regeneration. Dev cell 2013;25:478-491.

    10 Berg DA, Belnoue L, Song H et al. Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain. Development 2013;140:2548-2561.

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