Early life adversity in piglets induces long-term upregulation of the enteric cholinergic nervous system and heightened, sex-specific secretomotor neuron responses.
Early life adversity in piglets induces long-term upregulation of the enteric cholinergic nervous system and heightened, sex-specific secretomotor neuron responses.
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DOI：
10.1111/nmo.12828
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发表时间：
2016-09
影响因子：
3.5
通讯作者：
Moeser AJ
中科院分区：
文献类型：
--
作者：
Medland JE;Pohl CS;Edwards LL;Frandsen S;Bagley K;Li Y;Moeser AJ
早期生活逆境（ELA）是胃肠道（GI）疾病（如肠易激综合征（IBS））后期发病的危险因素;然而，其机制知之甚少。在这里，我们利用猪ELA模型，早期断奶应激（EWS），研究ELA对肠神经系统（ENS）的发育和功能的影响。雌性和去势雄性（雄性-C）仔猪在15日龄（EWS）或28日龄（晚期断奶对照; LWC）时从其母猪断奶。在60日龄和170日龄，回肠粘膜粘膜下层制剂安装在Ussing室和藜芦碱和促肾上腺皮质激素释放因子（CRF）诱发的短路电流（Isc）的反应被记录为分泌运动神经元功能的指标。肠神经元数量和选择的神经递质及其受体的表达也进行了测量。与LWC猪相比，雌性而非雄性C EWS猪在60日龄和170日龄时表现出更高的藜芦碱诱导的Isc反应，该反应可被河豚毒素（TTX）和阿托品阻断。来自EWS猪的肠神经元中胆碱乙酰转移酶阳性（ChAT+）的数量较多。在EWS猪中还观察到胆碱能信号传导增加的标志物（乙酰胆碱酯酶（AchE）增加和粘膜毒蕈碱受体3基因表达下调。这项研究表明，EWS在猪诱导持久的和性别特异性的超敏性的分泌运动神经元功能和上调的胆碱能ENS. These研究结果可能代表ELA和终身易感性胃肠道疾病，如肠易激综合征之间的机械联系。
Early life adversity (ELA) is a risk factor for the later-life onset of gastrointestinal (GI) diseases such as irritable bowel syndrome (IBS); however, the mechanisms are poorly understood. Here, we utilized a porcine model of ELA, early weaning stress (EWS), to investigate the influence of ELA on the development and function of the enteric nervous system (ENS). Female and castrated male (Male-C) piglets were weaned from their sow either at 15 d of age (EWS) or 28 d of age (late weaning control; LWC). At 60 d and 170 d of age, ileal mucosa-submucosa preparations were mounted in Ussing chambers and veratridine- and corticotropin releasing factor (CRF)-evoked short circuit current (Isc) responses were recorded as indices of secretomotor neuron function. Enteric neuron numbers and the expression of select neurotransmitters and their receptors were also measured. Compared with LWC pigs, female, but not Male-C EWS pigs exhibited heightened veratridine-induced Isc responses at 60 d and 170 d of age, that were blocked with tetrodotoxin (TTX) and atropine. Ileum from EWS pigs had higher numbers of enteric neurons that were choline acetyltransferase-positive (ChAT+). Markers of increased cholinergic signaling (increased acetylcholinesterase (AchE) and down-regulated mucosal muscarinic receptor 3 gene expression were also observed in EWS pigs. This study demonstrated that EWS in pigs induces lasting and sex-specific hypersensitivity of secretomotor neuron function and upregulation of the cholinergic ENS. These findings may represent a mechanistic link between ELA and lifelong susceptibility to GI diseases such as IBS.
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影响因子：
3.4
作者：
Agostini, Alessandro;Rizzello, Fernando;Campieri, Massimo
通讯作者：
Campieri, Massimo
DOI：
10.1007/7854_2010_112
发表时间：
2011-01-01
期刊：
MOLECULAR AND FUNCTIONAL MODELS IN NEUROPSYCHIATRY
影响因子：
--
作者：
Gieling, Elise T.;Schuurman, Teun;van der Staay, F. Josef
通讯作者：
van der Staay, F. Josef
影响因子：
3.4
作者：
Agostini, Alessandro;Rizzello, Fernando;Campieri, Massimo
通讯作者：
Campieri, Massimo
影响因子：
29.4
作者：
Ghia, Jean-Eric;Blennerhassett, Patricia;Collins, Stephen M.
通讯作者：
Collins, Stephen M.
影响因子：
4
作者：
Chaloner, Aaron;Greenwood-Van Meerveld, Beverley
通讯作者：
Greenwood-Van Meerveld, Beverley