Adrenocorticotropic hormone protects learning and memory function in epileptic Kcna1-null mice.

Adrenocorticotropic hormone protects learning and memory function in epileptic Kcna1-null mice.
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肾上腺皮质激素可保护癫痫KCNA1-NULL小鼠的学习和记忆功能。

DOI:
10.1016/j.neulet.2017.02.069
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发表时间:
2017-04-03
影响因子:
2.5
通讯作者:
Kim DY
Kim DY
中科院分区:
医学4区
文献类型:
--
作者:
Scantlebury MH;Chun KC;Ma SC;Rho JM;Kim DY

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ACTH是黑素皮质素多肽家族的一员,常用于治疗发育性癫痫性脑病谱系障碍,包括Ohtahara, West, Lennox Gastaut和Landau-Kleffner综合征以及电性癫痫持续状态睡眠。在这些疾病中,虽然ACTH通常能成功控制癫痫发作和/或间期脑电图异常,但ACTH是否具有独立于癫痫发作控制的其他有益作用尚不清楚。我们测试了ACTH是否可以改善癫痫Kcna1-null (KO)小鼠海马基于学习和记忆的内在损伤。我们发现ACTH -以Acthar凝胶形式给予,每天4次,剂量为4 IU/kg (16 IU/kg/天),连续7天-防止CA1海马高频刺激引起的长期增强(LTP)损伤,并恢复巴恩斯迷宫测试中的空间学习和记忆。然而,在这种治疗方案中,ACTH对自发性复发性癫痫发作的频率没有显著影响。总之,我们的研究结果表明,ACTH可以改善癫痫kcna1缺失小鼠的记忆障碍,并表明这种广泛使用的肽可能在癫痫大脑中发挥直接的促智作用。
ACTH, a member of the melanocortin family of peptides, is often used in the treatment of the developmental epileptic encephalopathy spectrum disorders including, Ohtahara, West, Lennox Gastaut and Landau-Kleffner Syndromes and electrical status epilepticus of sleep. In these disorders, although ACTH is often successful in controlling the seizures and/or inter-ictal EEG abnormalities, it is unknown whether ACTH possesses other beneficial effects independent of seizure control. We tested whether ACTH can ameliorate the intrinsic impairment of hippocampal-based learning and memory in epileptic Kcna1-null (KO) mice. We found that ACTH – administered in the form of Acthar Gel given i.p four times daily at a dose of 4 IU/kg (16 IU/kg/day) for 7 days – prevented impairment of long-term potentiation (LTP) evoked with high-frequency stimulation in CA1 hippocampus and also restored spatial learning and memory on the Barnes maze test. However, with this treatment regimen, ACTH did not exert a significant effect on the frequency of spontaneous recurrent seizures. Together, our findings indicate that ACTH can ameliorate memory impairment in epileptic Kcna1-null mice separate from seizure control, and suggest that this widely used peptide may exert direct nootropic effects in the epileptic brain.
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