Changes in enteric neurone phenotype and intestinal functions in a transgenic mouse model of enteric glia disruption
Changes in enteric neurone phenotype and intestinal functions in a transgenic mouse model of enteric glia disruption
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DOI：
10.1136/gut.2005.067595
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发表时间：
2006-05-01
期刊：
影响因子：
24.5
通讯作者：
Neunlist, M
中科院分区：
文献类型：
--
作者：
Aubé, AC;Cabarrocas, J;Neunlist, M
目的：肠胶质细胞对肠道功能调节的影响尚不清楚。我们的目的是确定肠神经胶质细胞改变模型中肠神经元的表型以及肠运动性和渗透性的推定变化。方法：采用在神经胶质细胞中表达血凝素（HA）的转基因小鼠。注射活化的HA特异性CD8+ T细胞诱导胶质细胞破坏。对照小鼠由注射活化的HA特异性CD8+ T细胞的非转基因雏鼠组成。对空肠粘膜下神经丛（SMP）和肌肠丛（MP）进行胆碱乙酰转移酶（ChAT）、P物质（SP）、血管活性肠肽（VIP）和一氧化氮合酶（NOS）的免疫组化染色。神经诱导的空肠肌活动在体外进行了表征。采用异硫氰酸-葡聚糖荧光素标记物测定胃肠道转运和细胞旁通透性。结果：转基因小鼠腹腔内可见CD3阳性T细胞浸润。在SMP中，转基因小鼠与对照小鼠相比，VIP和SP阳性神经元的比例降低。ChAT保持不变。在MP中，转基因小鼠的ChAT和NOS阳性神经元比例分别增加和减少。VIP和SP保持不变。转基因小鼠神经介导的空肠松弛程度低于对照组。在对照组小鼠中，n - g -硝基- l -精氨酸甲酯可减轻这种松弛，而在转基因小鼠中则无此作用。与对照组小鼠相比，转基因小鼠胃肠道转运延迟，肠道通透性增加。结论：神经胶质细胞破坏引起肠神经元神经化学编码的改变，这可能是肠运动和肠通透性功能障碍的部分原因。
Aims: The influence of enteric glia on the regulation of intestinal functions is unknown. Our aim was to determine the phenotype of enteric neurones in a model of glia alterations and the putative changes in intestinal motility and permeability.Methods: Transgenic mice expressing haemagglutinin (HA) in glia were used. Glia disruption was induced by injection of activated HA specific CD8+ T cells. Control mice consisted of non-transgenic littermates injected with activated HA specific CD8+ T cells. Immunohistochemical staining for choline acetyltransferase (ChAT), substance P (SP), vasoactive intestinal peptide (VIP), and nitric oxide synthase (NOS) was performed on jejunal submucosal plexus (SMP) and myenteric plexus (MP). Neurally induced jejunal muscle activity was characterised in vitro. Gastrointestinal transit and paracellular permeability were measured using fluorescein isothiocyanate-dextran markers.Results: CD3 positive T cells infiltrates were observed in the MP of transgenic mice. In the SMP, the proportions of VIP and SP positive neurones decreased in transgenic mice compared with control mice. ChAT remained unchanged. In the MP, the proportions of ChAT and NOS positive neurones increased and decreased, respectively, in transgenic mice. In contrast, VIP and SP remained unchanged. Neurally mediated jejunal relaxation was lower in transgenic mice than in controls. This relaxation was reduced by N-G-nitro-L-arginine methyl ester in control mice but not in transgenic mice. Gastrointestinal transit was delayed and intestinal permeability increased in transgenic mice compared with control mice.Conclusion: Glia disruption induces changes in the neurochemical coding of enteric neurones, which may partly be responsible for dysfunctions in intestinal motility and permeability.