Cholinergic Enhancement of Cell Proliferation in the Postnatal Neurogenic Niche of the Mammalian Spinal Cord
Cholinergic Enhancement of Cell Proliferation in the Postnatal Neurogenic Niche of the Mammalian Spinal Cord
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DOI：
10.1002/stem.2077
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发表时间：
2015-09-01
期刊：
影响因子：
5.2
通讯作者：
Deuchars, Susan A.
中科院分区：
文献类型：
--
作者：
Corns, Laura F.;Atkinson, Lucy;Deuchars, Susan A.
脊髓中央管（CC）周围的区域是一个高度可塑性的区域，被定义为产后神经原性龛。在该区域内是室管膜细胞，其可以在损伤后增殖和分化以形成新的星形胶质细胞和少突胶质细胞以及脑脊液接触细胞（CSFcC）。具体的环境条件，包括影响这些细胞及其增殖能力的神经递质的调节，是未知的。在这里，我们表明，乙酰胆碱促进小鼠室管膜细胞在体外和体内条件下的增殖。采用全细胞膜片钳技术，在急性脊髓切片上，乙酰胆碱直接使室管膜细胞和CSFcCs去极化。特异性烟碱乙酰胆碱受体（nAChR）拮抗剂的拮抗作用或含α 7 nAChR（α 7* nAChR）调节剂PNU 120596的增强作用表明，α 7* nAChR和非α 7* nAChR均介导胆碱能反应。使用核苷类似物EdU（5-乙炔基-2 '-脱氧尿苷）作为细胞增殖的标志物，在脊髓培养物中或体内应用α 7*-nAChR调节剂诱导CC区的增殖，产生表达Sox-2的室管膜细胞。在白色和灰质中增殖也增加。PNU 120596给药还增加了共表达少突胶质细胞标志物的细胞比例。因此，乙酰胆碱可用性的变化可以通过α 7* nAChR调节室管膜细胞层和白色和灰质中细胞的增殖速率。这项研究强调了需要进一步研究神经递质如何调节脊髓对损伤或衰老的反应。
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 that 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 depolarized ependymal cells and CSFcCs. Antagonism by specific nicotinic acetylcholine receptor (nAChR) antagonists or potentiation by the alpha 7 containing nAChR (alpha 7* nAChR) modulator PNU 120596 revealed that both alpha 7*nAChRs and non-alpha 7*nAChRs mediated the cholinergic responses. Using the nucleoside analogue EdU (5-ethynyl-2'-deoxyuridine) as a marker of cell proliferation, application of alpha 7*-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 and grey matter through alpha 7*nAChRs. This study highlights the need for further investigation into how neurotransmitters regulate the response of the spinal cord to injury or during aging.