期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2000
卷号：97
期号：22
页码：12312-12317
DOI：10.1073/pnas.97.22.12312
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Seizure activity regulates gene expression for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), and their receptor components, the transmembrane c-Ret tyrosine kinase and the glycosylphosphatidylinositol-anchored GDNF family receptor (GFR) 1 and 2 in limbic structures. We demonstrate here that epileptogenesis, as assessed in the hippocampal kindling model, is markedly suppressed in mice lacking GFR2. Moreover, at 6 to 8 wk after having reached the epileptic state, the hyperexcitability is lower in GFR2 knock-out mice as compared with wild-type mice. These results provide evidence that signaling through GFR2 is involved in mechanisms regulating the development and persistence of kindling epilepsy. Our data suggest that GDNF and NRTN may modulate seizure susceptibility by altering the function of hilar neuropeptide Y-containing interneurons and entorhinal cortical afferents at dentate granule cell synapses.
