Berthoud H R, Patterson L M, Zheng H
Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA.
Anat Rec. 2001 Jan 1;262(1):29-40. doi: 10.1002/1097-0185(20010101)262:1<29::AID-AR1008>3.0.CO;2-B.
Many gastrointestinal and pancreatic functions are under strong modulatory control by the brain via the vagus nerve. To start identifying location and neurochemical phenotype of the enteric neurons receiving functional vagal efferent input, we activated vagal preganglionic neurons either by electrical or chemical stimulation and examined the expression of phosphorylated CREB (c-AMP response element binding protein) and the immediate early gene c-Fos. There was no spontaneous expression of both markers in the pancreas and considerable spontaneous expression of p-CREB but not Fos in the upper GI-tract. Unilateral electrical vagal stimulation-induced p-CREB was found in 40% of neurons in the head of the pancreas. Fos expression was found in 70-90% of neurons in the esophagus and stomach, in 20-30% of myenteric plexus neurons and 5-15% in submucosal neurons of the proximal duodenum. Double-labeling experiments showed that a majority of pancreatic neurons and about 25-35% of neurons in the stomach and duodenum contain NADPH-diaphorase and that many of these receive functional vagal input. Other neurons that can be vagally activated contain gastrin-releasing peptide or calretinin. Chemical stimulation of the dorsal surface of the caudal brainstem with the stable TRH analog RX77368 resulted in selective activation of vagal efferents with expression of Fos in a small number of gastric myenteric plexus neurons. The results demonstrate the suitability of this method to investigate magnitude and local distribution of vagal input to the enteric nervous system as well as specificity of its neurochemically coded pathways. They represent the first step in the identification of function-specific units of parasympathetic vagal outflow.
许多胃肠和胰腺功能受到大脑通过迷走神经的强大调节控制。为了开始确定接受功能性迷走神经传出输入的肠神经元的位置和神经化学表型，我们通过电刺激或化学刺激激活迷走神经节前神经元，并检测磷酸化CREB（c-AMP反应元件结合蛋白）和即刻早期基因c-Fos的表达。在胰腺中这两种标记物均无自发表达，在上消化道中p-CREB有相当程度的自发表达，但Fos没有。单侧电刺激迷走神经诱导的p-CREB在胰腺头部40%的神经元中被发现。Fos表达在食管和胃中70%-90%的神经元中被发现，在肌间神经丛神经元中为20%-30%，在十二指肠近端黏膜下神经元中为5%-15%。双重标记实验表明，大多数胰腺神经元以及胃和十二指肠中约25%-35%的神经元含有NADPH-黄递酶，并且其中许多接受功能性迷走神经输入。其他可被迷走神经激活的神经元含有胃泌素释放肽或钙视网膜蛋白。用稳定的促甲状腺激素类似物RX77368对脑桥尾端背表面进行化学刺激，导致迷走神经传出纤维选择性激活，少数胃肌间神经丛神经元中有Fos表达。结果证明了该方法适用于研究迷走神经输入到肠神经系统的强度和局部分布及其神经化学编码通路的特异性。它们代表了识别副交感迷走神经传出功能特异性单位的第一步。
