Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem
Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem
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DOI：
10.1016/s0306-4522(96)00434-4
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发表时间：
1997-03-01
期刊：
影响因子：
3.3
通讯作者：
Orskov, C
中科院分区：
文献类型：
--
作者：
Larsen, PJ;TangChristensen, M;Orskov, C
中央给药胰高血糖素前体衍生肽胰高血糖素样肽-1显著抑制食物和水的摄入，胰高血糖素样肽-1结合位点存在于参与摄入行为调节的众多中心区域。为了进一步评估含有中枢胰高血糖素样肽-1的神经元回路的神经解剖学组织及其对摄入行为的潜在影响，我们在大鼠身上进行了一系列实验，展示了胰高血糖素前体前体合成和加工的地形位置，然后对加工片段进行了色谱分析。原位杂交组织化学显示编码信使RNA的胰高血糖素前原在孤立束核尾侧的单个神经元群中表达。下丘脑和脑干组织提取物的凝胶色谱分析显示，胰高血糖素前体的加工方式与小肠相似，优先产生胰高血糖素样肽-1和胰高血糖素样肽-2。胰高血糖素样肽-1合成的单一脑位点随后通过免疫组织化学证实，胰高血糖素样肽-l免疫反应性核周位于孤立束核的中央和尾侧。然而，在前脑包括下丘脑、丘脑和皮质区发现了许多含有胰高血糖素样肽-1免疫反应纤维的位点。最密集的胰高血糖素样肽-1免疫反应神经纤维分布于下丘脑背内侧核和室旁核，但第三脑室室周层也可见大量胰高血糖素样肽-1免疫反应神经纤维。酪氨酸羟化酶和胰高血糖素样肽-1双标记免疫组化未发现儿茶酚胺和胰高血糖素样肽-1在下脑干神经元共定位的证据。为了识别投射到下丘脑室旁核的孤立束核的神经元，将逆行示踪剂fluorgold注射到下丘脑靶点，并在含有逆行标记的核周围的脑干部分上进行胰高血糖素样肽-1和酪氨酸羟化酶阳性神经元的双重免疫细胞化学鉴定。从本实验中可以看出，孤立束核中央部分的许多逆行标记神经元具有儿茶酚胺能，而没有胰高血糖素样肽-1免疫反应。相反，大多数孤束核尾侧逆行标记的神经元含有胰高血糖素样肽-1。这些观察结果进一步证实，孤立束的胰高血糖素样肽-1神经元构成了一个独特的非儿茶酚胺能细胞群，它投射到许多靶点，其中一个靶点是下丘脑室旁核。版权所有IBRO。
Central administration of the preproglucagon-derived peptide glucagon-like peptide-1 significantly inhibits ingestion of food and water, and glucagon-like peptide-1 binding sites are present in a multitude of central areas involved in the regulation of ingestional behaviour. To evaluate further the neuroanatomical organization of central glucagon-like peptide-1 containing neuronal circuits with potential implications on ingestional behaviour, we carried out a series of experiments in the rat demonstrating the topographical sites of synthesis and processing of the preproglucagon precursor followed by a chromatographic analysis of the processed fragments. In situ hybridization histochemistry revealed that preproglucagon encoding messenger RNA was expressed in a single population of neurons in the caudal portion of the nucleus of the solitary tract. Gel chromatographic analysis of hypothalamic and brainstem tissue extracts revealed that the preproglucagon precursor is processed in a fashion similar to that seen in the small intestine, preferentially giving rise to glicentin, glucagon-like peptide-1 and glucagon-like peptide-2. This single brain site of glucagon-like peptide-1 synthesis was subsequently confirmed by immunohistochemical demonstration of glucagon-like peptide-l-immunoreactive perikarya in the central and caudal parts of the nucleus of the solitary tract. Numerous sites containing glucagon-like peptide-1 immunoreactive fibres were, however, discovered in the forebrain including hypothalamic, thalamic and cortical areas. The densest innervation by glucagon-like peptide-1 immunoreactive nerve fibres was seen in the hypothalamic dorsomedial and paraventricular nuclei, but numerous glucagon-like peptide-1 immunoreactive fibres were also seen throughout the periventricular strata of the third ventricle. Dual-labelling immunohistochemistry for tyrosine hydroxylase and glucagon-like peptide-1 gave no evidence for co-localization of catecholamines and glucagon-like peptide-1 in neurons of the lower brainstem. To identify neurons of the nucleus of the solitary tract that project to the hypothalamic paraventricular nucleus, the retrograde tracer FluoroGold was injected into this hypothalamic target and dual immunocytochemical identification of glucagon-like peptide-1 and tyrosine hydroxylase-positive neurons was performed on brainstem sections containing retrogradely labelled perikarya. From this experiment it was seen that many of the retrogradely labelled neurons in the central portion of the nucleus of the solitary tract are catecholaminergic, while none is glucagon-like peptide-1 immunoreactive. In contrast, most of the retrogradely labelled neurons of the caudal portion of the nucleus of the solitary tract contain glucagon-like peptide-1.These observations further substantiate that glucagon-like peptide-1 neurons of the solitary tract constitute a distinct non-catecholaminergic cell group which projects to many targets, one of which is the hypothalamic paraventricular nucleus. Copyright (C) 1997 IBRO.