Plastische Ver?nderungen vonNeuropeptiden bei Patienten mitTemporallappenepilepsie

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• 作者：Susanne Pirker ^{A1 A3} ; Thomas Czech ^A2 ; Christoph Baumgartner ^A1 ; Sabine Fü ; rtinger ^A3 ; Anna Wieselthaler ^A3 ; Elisabeth Gasser ^A3
• 关键词：Neuropeptide ; temporal lobe epilepsy ; neuropeptide Y ; dynorphin ; chromogranin
• 刊名：Zeitschrift fr Epileptologie
• 出版年：2003
• 出版时间：August2003
• 年：2003
• 卷：16
• 期：3
• 页码：235-242
• 全文大小：373 KB

文摘

Neuropeptides are stored together with the classical neurotransmitter in large dense core vesicles from where they are released upon stimulation. In animal models, neuropeptides have been shown to influence neuronal excitability. For example, an anticonvulsive action was found for neuropeptide Y (NPY), galanin, dynorphin and somatostatin. By contrast, substance P was found to have a proconvulsive action. We investigated the expression of NPY, dynorphin, secretoneurin and chromogranin B in hippocampi from patients with intractable temporal lobe epilepsy (TLE) (n=29; mean age=34.5 years; mean duration of epilepsy=21.4 years) and post mortem controls (n=21; mean age=57.7 years; mean post mortem delay=17.2 hours). In situ hybridization for dynorphin showed a marked increase of mRNA expression in granule cells of the dentate gyrus. For NPY, we found increased mRNA expression in hilar interneurons. Immunohistochemical staining showed a sprouting of neuropeptide-containing axons. Antibodies for dynorphin, secretoneurin and chromogranin B labeled mossy fiber terminals in the inner molecular layer of the denate gyrus of patients with, but not without, hippocampal sclerosis. NPY- and secretoneurin-containing interneurons revealed a dense plexus of fibers in the molecular layer and the hilus of the dentate gyrus as well as in stratum lucidum, the terminal field of mossy fibers. Radioligand binding to the NPY Y2 receptor, which mediates anticonvulsive actions of NPY, was increased in the hippocampus of TLE patients. In summary, our data show a marked reorganization of hippocampal circuits and an upregulation of the expression of dynorphin, NPY and the Y2 receptor in the epileptic hippocampus. These changes may contribute to endogenous anticonvulsive mechanisms in TLE patients.