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对源自腹腔的结状神经节和背根神经节中鼠类感觉神经元的分子特征分析

Molecular profiling of murine sensory neurons in the nodose and dorsal root ganglia labeled from the peritoneal cavity.

作者信息

Peeters Pieter J, Aerssens Jeroen, de Hoogt Ronald, Stanisz Andrzej, Göhlmann Hinrich W, Hillsley Kirk, Meulemans Ann, Grundy David, Stead Ronald H, Coulie Bernard

机构信息

Department of Internal Medicine, Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium.

出版信息

Physiol Genomics. 2006 Feb 14;24(3):252-63. doi: 10.1152/physiolgenomics.00169.2005. Epub 2005 Nov 22.

Abstract

Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. To elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488-conjugated cholera toxin B allowed enrichment for neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser-capture microdissection. Gene expression profiles of these afferent neurons, obtained by microarray hybridization, were analyzed using multivariate spectral map analysis, significance analysis of microarrays (SAM) algorithm, and fold-difference filtering. A total of 1,996 genes were differentially expressed in DRG vs. NG, including 41 G protein-coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia, demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, we provide a detailed catalog of all adrenergic and cholinergic, GABA, glutamate, serotonin, and dopamine receptors; voltage-gated potassium, sodium, and calcium channels; and transient receptor potential cation channels present in afferents projecting to the peritoneal cavity. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacological agents modulating visceral sensation.

摘要

迷走传入神经元主要传递生理信息,而脊髓传入神经将来自内脏的有害信号传递至中枢神经系统。为阐明这些不同特性的分子特征,我们比较了小鼠结节神经节(NG)和背根神经节(DRG)中神经元的基因表达谱。腹腔注射Alexa Fluor - 488偶联的霍乱毒素B可富集投射至内脏的神经元。使用激光捕获显微切割技术分离DRG(T10至T13)和NG中的荧光神经元。通过微阵列杂交获得的这些传入神经元的基因表达谱,使用多变量谱图分析、微阵列显著性分析(SAM)算法和倍数差异过滤进行分析。DRG与NG中共有1996个基因差异表达,包括41个G蛋白偶联受体和60个离子通道。激光捕获神经元获得的表达谱与整个神经节获得的表达谱形成对比,显示出显著差异,并且在研究内脏感觉神经元时由于体感觉神经元对信号的稀释而需要进行显微切割。此外,我们提供了所有肾上腺素能、胆碱能、GABA、谷氨酸、5-羟色胺和多巴胺受体;电压门控钾、钠和钙通道;以及投射至腹膜腔的传入神经中存在的瞬时受体电位阳离子通道的详细目录。我们的全基因组表达谱数据为NG和DRG感觉神经元之间功能差异和相似性的分子特征提供了新的见解。此外,这些发现将为调节内脏感觉的药物作用模式提供新的见解。

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