Insulin growth factor-1 (IGF-1) enhances hippocampal excitatory and seizure activity through IGF-1 receptor-mediated mechanisms in the epileptic brain
Insulin growth factor-1 (IGF-1) enhances hippocampal excitatory and seizure activity through IGF-1 receptor-mediated mechanisms in the epileptic brain
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胰岛素生长因子-1 (IGF-1) 通过癫痫脑中 IGF-1 受体介导的机制增强海马兴奋性和癫痫发作活动。
DOI：
10.1042/cs20150312
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发表时间：
2015-12-01
期刊：
影响因子：
6
通讯作者：
Wang, Xuefeng
中科院分区：
文献类型：
--
作者：
Jiang, Guohui;Wang, Wei;Wang, Xuefeng
已知胰岛素样生长因子-1（IGF-1）促进神经发生和存活。然而，最近的研究表明，IGF-1调节神经元放电和兴奋性神经传递。在目前的研究中，专注于颞叶癫痫，我们发现，IGF-1水平和IGF-1受体激活的增加，在人类癫痫组织，毛果芸香碱和戊四唑治疗的大鼠模型。使用急性癫痫发作模型，我们表明，侧脑室注射IGF-1升高IGF-1受体（IGF-1 R）信号之前，毛果芸香碱应用具有促惊厥作用。在体内脑电图记录和功率谱分析的局部场电位显示，IGF-1促进癫痫样活动。这种作用通过IGF-1 R抑制剂的共同应用而减弱。在体外电生理研究中，我们证明IGF-1增强兴奋性神经传递和α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸受体和N-甲基-D-天冬氨酸受体介导的电流被IGF-1 R抑制剂抑制。最后，外源性IGF-1增加大鼠癫痫发作中细胞外信号相关激酶（ERK）-1/2和蛋白激酶B（Akt）的激活，而苦鬼脂素则减少。一项行为学研究表明，ERK 1/2或Akt抑制剂可减弱癫痫发作活动。这些结果表明，增加IGF-1水平后，海马神经元放电，反过来，可能会促进癫痫发作活动，通过IGF-1 R依赖的机制。本研究提出了一个以前未得到重视的作用IGF-1 R在癫痫发作活动的发展。
Insulin-like growth factor-1 (IGF-1) is known to promote neurogenesis and survival. However, recent studies have suggested that IGF-1 regulates neuronal firing and excitatory neurotransmission. In the present study, focusing on temporal lobe epilepsy, we found that IGF-1 levels and IGF-1 receptor activation are increased in human epileptogenic tissues, and pilocarpine-and pentylenetetrazole-treated rat models. Using an acute model of seizures, we showed that lateral cerebroventricular infusion of IGF-1 elevates IGF-1 receptor (IGF-1R) signalling before pilocarpine application had proconvulsant effects. In vivo electroencephalogram recordings and power spectrogram analysis of local field potential revealed that IGF-1 promotes epileptiform activities. This effect is diminished by co-application of an IGF-1R inhibitor. In an in vitro electrophysiological study, we demonstrated that IGF-1 enhancement of excitatory neurotransmission and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor-and N-methyl-D-aspartate receptor-mediated currents is inhibited by IGF-1R inhibitor. Finally, activation of extracellular signal-related kinase (ERK)-1/2 and protein kinase B (Akt) in seizures in rats is increased by exogenous IGF-1 and diminished by picropodophyllin. A behavioural study reveals that the ERK1/2 or Akt inhibitor attenuates seizure activity. These results indicate that increased IGF-1 levels after recurrent hippocampal neuronal firings might, in turn, promote seizure activity via IGF-1R-dependent mechanisms. The present study presents a previously unappreciated role of IGF-1R in the development of seizure activity.