Kanter R K, Erickson J T, Millhorn D E
Department of Physiology, University of North Carolina, Chapel Hill 27599.
Exp Neurol. 1994 Oct;129(2):290-8. doi: 10.1006/exnr.1994.1171.
We performed studies to determine the anatomical regions and chemical phenotypes of neurons within the rat medulla oblongata activated by pentylenetetrazole-induced seizures. Activated cells were identified by their expression of the c-fos gene, detected by in situ hybridization for c-fos mRNA and immunocytochemistry for Fos protein. Activated cells were located predominantly in nucleus tractus solitarius (NTS), with c-fos mRNA appearing within 20 min after seizures (peak at 1-2 h), followed by Fos immunoreactivity visible at 1 h (peak at 2-4 h). Neither nonspecific noxious stimulation by intraperitoneal injection of saline nor brief exposure to hypoxic or hypercapnic gas mixtures to stimulate chemoreceptors reproduced this pattern of labeling. Prodynorphin or proenkephalin mRNA, detected by in situ hybridization, was colocalized with Fos immunoreactivity in many NTS cells. Thus, seizures activate neuronal pathways in the medulla oblongata which express genes for endogenous opioids. Potential long-term effects of seizures are suggested by the in situ hybridization finding that NTS prodynorphin mRNA increased 24 h after seizures compared to control levels.
我们进行了多项研究，以确定戊四氮诱发癫痫发作时大鼠延髓内被激活的神经元的解剖区域和化学表型。通过原位杂交检测c-fos mRNA以及免疫细胞化学检测Fos蛋白，根据c-fos基因的表达来识别被激活的细胞。被激活的细胞主要位于孤束核（NTS），癫痫发作后20分钟内出现c-fos mRNA（1-2小时达到峰值），随后在1小时可见Fos免疫反应性（2-4小时达到峰值）。腹腔注射生理盐水的非特异性有害刺激，或短暂暴露于低氧或高碳酸气体混合物以刺激化学感受器，均未重现这种标记模式。通过原位杂交检测到的前强啡肽或前脑啡肽mRNA，在许多NTS细胞中与Fos免疫反应性共定位。因此，癫痫发作激活了延髓中表达内源性阿片类物质基因的神经元通路。原位杂交结果表明，与对照水平相比，癫痫发作后24小时NTS前强啡肽mRNA增加，提示癫痫发作可能存在潜在的长期影响。
