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Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice
BMC Neuroscience ( IF 2.4 ) Pub Date : 2021-01-15 , DOI: 10.1186/s12868-020-00606-z
Xin-Ming Luo 1, 2 , Jing Zhao 1 , Wen-Yue Wu 1 , Jie Fu 1 , Zheng-Yu Li 1 , Ming Zhang 1 , Jie Lu 1
Affiliation  

Background Status epilepticus (SE) is a life-threatening neurological disorder. The hippocampus, as an important area of the brain that regulates cognitive function, is usually damaged after SE, and cognitive deficits often result from hippocampal neurons lost after SE. Fyn, a non-receptor Src family of tyrosine kinases, is potentially associated with the onset of seizure. Saracatinib, a Fyn inhibitor, suppresses epileptogenesis and reduces epileptiform spikes. However, whether saracatinib inhibits cognitive deficits after SE is still unknown. Methods In the present study, a pilocarpine-induced SE mouse model was used to answer this question by using the Morris water maze and normal object recognition behavioral tests. Results We found that saracatinib inhibited the loss in cognitive function following SE. Furthermore, we found that the number of hippocampal neurons in the saracatinib treatment group was increased, when compared to the SE group. Conclusions These results showed that saracatinib can improve cognitive functions by reducing the loss of hippocampal neurons after SE, suggesting that Fyn dysfunction is involved in cognitive deficits after SE, and that the inhibition of Fyn is a possible treatment to improve cognitive function in SE patients.

中文翻译:

使用 Fyn 抑制剂萨拉卡替尼治疗癫痫持续状态后可改善小鼠的认知功能

背景癫痫持续状态 (SE) 是一种危及生命的神经系统疾病。海马体作为大脑中调节认知功能的重要区域,在 SE 后通常会受到损伤,而 SE 后海马神经元丢失通常会导致认知缺陷。Fyn 是酪氨酸激酶的非受体 Src 家族,可能与癫痫发作有关。Saracatinib 是一种 Fyn 抑制剂,可抑制癫痫发生并减少癫痫样尖峰。然而,萨拉卡替尼是否能抑制 SE 后的认知缺陷仍然未知。方法在本研究中,毛果芸香碱诱导的 SE 小鼠模型通过使用莫里斯水迷宫和正常物体识别行为测试来回答这个问题。结果我们发现萨拉卡替尼抑制了 SE 后认知功能的丧失。此外,我们发现,与 SE 组相比,萨拉卡替尼治疗组的海马神经元数量增加。结论 这些结果表明,saracatinib 可以通过减少 SE 后海马神经元的损失来改善认知功能,表明 Fyn 功能障碍与 SE 后的认知缺陷有关,并且抑制 Fyn 是改善 SE 患者认知功能的一种可能的治疗方法。
更新日期:2021-01-15
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