Postnatal development of myenteric neurochemical phenotype and impact on neuromuscular transmission in the rat colon
Postnatal development of myenteric neurochemical phenotype and impact on neuromuscular transmission in the rat colon
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DOI：
10.1152/ajpgi.00092.2010
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发表时间：
2010-08-01
影响因子：
4.5
通讯作者：
Neunlist, M.
中科院分区：
文献类型：
--
作者：
de Vries, P.;Soret, R.;Neunlist, M.
De Vries P，Soret R，Suply E，Heloury Y，Neunlist M.出生后大鼠结肠肌间神经化学表型的发展及其对神经肌肉传递的影响。Am J Physiol胃肠病肝生理学299：G539-G547,2010。2010年6月3日首次出版；DOI：10.1152/ajpgi.00092.2010。-出生后肠道运动发生深刻变化，但胃肠道(GI)运动的关键调节因子-肠道神经系统(ENS)在这些变化中的参与在很大程度上仍不清楚。因此，我们研究了ENS表型的出生后发育，并确定了它对大鼠结肠神经肌肉传递的功能反应。分别于出生后第1天、第3天、第5天、第7天、第14天、第21天和第36天处死SD大鼠。用抗胆碱乙酰转移酶(ChAT)、神经元型一氧化氮合酶(NNOS)和Huc/D的抗体对整个结肠肌间神经丛进行染色，在器官室内观察电场刺激(EFS)诱导的结肠收缩反应。通过测量结肠小球潜伏期时间来评估体内的运动能力。随机发生的体外收缩从P5开始出现。从P14开始，出现节律性阶段性收缩，其频率和幅度随着时间的推移而增加。在体内，珠潜伏期在P14和P21之间显著缩短。在体外，EFS诱导的收缩反应随着时间的推移而显著增加，并在P14开始被阿托品显著降低，但只有在P21之后才对L-NAME敏感。从P14开始，ChAT免疫反应(IR)神经元的比例呈时间依赖性地增加。与P1相比，nNOS阳性神经元的比例早在P5时就增加了，但此后没有变化。我们的数据支持胆碱能肌间通路在出生后运动发育中的关键作用，并进一步确定它们是治疗新生儿胃肠动力障碍的假定治疗靶点。
de Vries P, Soret R, Suply E, Heloury Y, Neunlist M. Postnatal development of myenteric neurochemical phenotype and impact on neuromuscular transmission in the rat colon. Am J Physiol Gastrointest Liver Physiol 299: G539-G547, 2010. First published June 3, 2010; doi: 10.1152/ajpgi.00092.2010.-Profound changes in intestinal motility occur during the postnatal period, but the involvement of the enteric nervous system (ENS), a key regulator of gastrointestinal (GI) motility, in these modifications remains largely unknown. We therefore investigated the postnatal development of the ENS phenotype and determined its functional repercussion on the neuromuscular transmission in the rat colon. Sprague-Dawley rats were euthanized at postnatal day (P) 1, P3, P5, P7, P14, P21, and P36. Whole mounts of colonic myenteric plexus were stained with antibodies against choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and HuC/D. Colonic contractile response induced by electrical field stimulation (EFS) was investigated in organ chambers in absence or presence of N-nitro-L-arginine methyl ester (L-NAME) and/or atropine. In vivo motility was assessed by measurement of the colonic bead latency time. Randomly occurring ex vivo contractions appeared starting at P5. Starting at P14, rhythmic phasic contractions occurred whose frequency and amplitude increased over time. In vivo, bead latency was significantly reduced between P14 and P21. Ex vivo, EFS-induced contractile responses increased significantly over time and were significantly reduced by atropine starting at P14 but were sensitive to L-NAME only after P21. The proportion of ChAT-immunoreactive (IR) neurons increased time dependently starting at P14. The proportion of nNOS-IR neurons increased as early as P5 compared with P1 but did not change afterward. Our data support a key role for cholinergic myenteric pathways in the development of postnatal motility and further identify them as putative therapeutic target for the treatment of GI motility disorders in the newborn.