Suppression of c-Kit signaling induces adult neurogenesis in the mouse intestine after myenteric plexus ablation with benzalkonium chloride.
Suppression of c-Kit signaling induces adult neurogenesis in the mouse intestine after myenteric plexus ablation with benzalkonium chloride.
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DOI：
10.1038/srep32100
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发表时间：
2016-08-30
影响因子：
4.6
通讯作者：
Kiyama H
中科院分区：
文献类型：
--
作者：
Tamada H;Kiyama H
成人神经发生很少发生在肠神经系统（ENS）。在这项研究中，我们证明，在用苯扎氯铵（BAC）消融肠肌丛（MP）后，c-kit功能丧失突变小鼠（W/Wv）的ENS中显着诱导成年神经发生。BAC处理后，大鼠中几乎所有神经元和纤维消失。然而，消融后1周，野生型和W/Wv小鼠的MP、纵肌和浆膜下层均观察到大量神经纤维从未受损区域穿透。BAC处理2周后，W/Wv小鼠的浆膜下和纵肌层中除了穿透纤维外，还出现了大量异位神经元，而野生型小鼠仅出现少量异位神经元。这些异位神经元表达兴奋性或抑制性内在运动神经元标记物，并形成神经节样结构，包括胶质细胞、突触囊泡和基底层。此外，口服伊马替尼（一种c-Kit抑制剂和胃肠道间质肿瘤的抗癌剂）在BAC治疗后显著诱导异位神经元的出现，即使在野生型小鼠中也是如此。这些结果表明，在体内，成人神经发生受c-Kit信号的负调控。
Adult neurogenesis rarely occurs in the enteric nervous system (ENS). In this study, we demonstrated that, after intestinal myenteric plexus (MP) ablation with benzalkonium chloride (BAC), adult neurogenesis in the ENS was significantly induced in c-kit loss-of-function mutant mice (W/Wv). Almost all neurons and fibers in the MP disappeared after BAC treatment. However, 1 week after ablation, substantial penetration of nerve fibers from the non-damaged area was observed in the MP, longitudinal muscle and subserosal layers in both wildtype and W/Wv mice. Two weeks after BAC treatment, in addition to the penetrating fibers, a substantial number of ectopic neurons appeared in the subserosal and longitudinal muscle layers of W/Wv mice, whereas only a few ectopic neurons appeared in wildtype mice. Such ectopic neurons expressed either excitatory or inhibitory intrinsic motor neuron markers and formed ganglion-like structures, including glial cells, synaptic vesicles and basal lamina. Furthermore, oral administration of imatinib, an inhibitor of c-Kit and an anticancer agent for gastrointestinal stromal tumors, markedly induced appearance of ectopic neurons after BAC treatment, even in wildtype mice. These results suggest that adult neurogenesis in the ENS is negatively regulated by c-Kit signaling in vivo.
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影响因子：
15.9
作者：
Laranjeira, Catia;Sandgren, Katarina;Pachnis, Vassilis
通讯作者：
Pachnis, Vassilis
影响因子：
3.7
作者：
Goto K;Kato G;Kawahara I;Luo Y;Obata K;Misawa H;Ishikawa T;Kuniyasu H;Nabekura J;Takaki M
通讯作者：
Takaki M
影响因子：
2.5
作者：
PHAM, TD;GERSHON, MD;ROTHMAN, TP
通讯作者：
ROTHMAN, TP
DOI：
10.1523/jneurosci.1145-09.2009
发表时间：
2009-08-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Liu MT;Kuan YH;Wang J;Hen R;Gershon MD
通讯作者：
Gershon MD
影响因子：
11.4
作者：
NOCKA, K;BUCK, J;BESMER, P
通讯作者：
BESMER, P