Humpel C, Hoffer B, Strömberg I, Bektesh S, Collins F, Olson L
Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Neuroscience. 1994 Apr;59(4):791-5. doi: 10.1016/0306-4522(94)90284-4.
Glial cell line-derived neurotrophic factor (GDNF) is a novel member of the transforming growth factor-beta superfamily with potent trophic effects on dopamine neurons. Kainate-induced epileptic seizures have been shown to induce gene expression of trophic factors, particularly members of neurotrophin or fibroblast growth factor families, in the hippocampus. In this study, we examined the effects of kainate (12 mg/kg, i.p.)-induced epileptic seizures on the expression of the novel neurotrophic factor GDNF in the hippocampus. While GDNF messenger RNA was not detected during development or in normal adult rats in the hippocampus, kainate-induced epileptic seizures markedly increased GDNF messenger RNA in scattered neurons in the dentate granule layer 3 h after injection. Six hours after kainate almost all dentate granule cells and expressed GDNF messenger RNA. The increase in GDNF messenger RNA in the dentate granule layer returned almost to control levels 24 h after kainate; however, there was still expression of GDNF messenger RNA in the hilus/CA4 and also in pyramidal neurons in areas CA1-CA3. We conclude that GDNF messenger RNA is regulated, in part, via glutamate-mediated excitation and may play a role in long-lasting structural and/or functional reorganization in the hippocampal formation.
胶质细胞系源性神经营养因子（GDNF）是转化生长因子-β超家族的一个新成员，对多巴胺能神经元具有强大的营养作用。已有研究表明，海藻酸诱导的癫痫发作可诱导海马中营养因子的基因表达，特别是神经营养因子或成纤维细胞生长因子家族的成员。在本研究中，我们检测了海藻酸（12mg/kg，腹腔注射）诱导的癫痫发作对海马中新型神经营养因子GDNF表达的影响。虽然在发育过程中或正常成年大鼠的海马中未检测到GDNF信使核糖核酸，但海藻酸诱导的癫痫发作在注射后3小时使齿状颗粒层中散在神经元的GDNF信使核糖核酸显著增加。海藻酸注射6小时后，几乎所有齿状颗粒细胞都表达了GDNF信使核糖核酸。齿状颗粒层中GDNF信使核糖核酸的增加在海藻酸注射后24小时几乎恢复到对照水平；然而，在海马回/CA4区以及CA1-CA3区的锥体神经元中仍有GDNF信使核糖核酸的表达。我们得出结论，GDNF信使核糖核酸部分通过谷氨酸介导的兴奋进行调节，并可能在海马结构的长期结构和/或功能重组中发挥作用。
