Low-dose intranasal insulin improves cognitive function and suppresses the development of epilepsy
Low-dose intranasal insulin improves cognitive function and suppresses the development of epilepsy
复制标题
低剂量鼻内胰岛素可改善认知功能并抑制癫痫的发展
DOI：
10.1016/j.brainres.2019.146474
复制
发表时间：
2020-01-01
期刊：
影响因子：
2.9
通讯作者：
Jiang, Guohui
中科院分区：
文献类型：
--
作者：
Peng, Shu;Yang, Jin;Jiang, Guohui
鼻内胰岛素在多种神经系统疾病中发挥神经保护作用。然而，鼻内胰岛素是否影响癫痫活动以及它是否在癫痫疾病中具有神经保护作用仍然是未知的。在这项研究中，我们表明，低剂量鼻内胰岛素抑制红藻氨酸（KA）或戊四唑（PTZ）诱导的急性癫痫发作和减少癫痫放电活动的小鼠，可能是通过减轻增加的谷氨酸诱导的海马。同时，鼻内胰岛素可增加GABA水平和海马theta区的活性，可能影响海马的兴奋性。在慢性KA诱导的癫痫中，低剂量鼻内胰岛素降低自发复发性癫痫发作和癫痫放电的频率，同时增加θ能量，从而改善空间记忆。较大剂量的鼻内胰岛素增加了癫痫发作的频率，但没有加重认知功能障碍，这表明癫痫发作的频率可能与认知功能障碍无关。总之，我们的研究结果表明，低剂量鼻内胰岛素抑制癫痫事件，改善癫痫小鼠的认知障碍，表明鼻内胰岛素可以改善学习和记忆。然而，更大的剂量可能会增加癫痫发作的风险。
Intranasal insulin exerts neuroprotective effects in a variety of neurological diseases. Whether intranasal insulin affects epileptic activity and whether it has neuroprotective effects in epileptic diseases is however still unknown. In this study we show that low-dose intranasal insulin inhibited kainic acid (KA)- or pentylenetetrazole (PTZ)-induced acute seizures and reduced epileptic discharge activities in mice, potentially by alleviating the increase in seizure-induced glutamate in the hippocampus. Meanwhile, intranasal insulin increased GABA levels and the activities of hippocampal theta, which may affect the excitability of the hippocampus. In chronic KA-induced epilepsy, low-dose intranasal insulin reduces the frequency of spontaneous recurrent seizures and epileptic discharges, while it increases theta energy and thereby improves spatial memory. Larger doses of intranasal insulin increased the frequency of seizures but did not aggravate cognitive impairment, suggesting that the frequency of seizures may not be related to impaired cognitive function. Overall, our findings show that low-dose intranasal insulin inhibits epileptic events and improves cognitive impairment in epileptic mice, suggesting that learning and memory can be improved by intranasal insulin. However, larger doses might increase the risk of epileptic seizures.