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

作者：Scantlebury Morris H; Chun Kyoung Chul; Ma Shun Chieh; Rho Jong M; Kim Do Young^*

来源：Neuroscience Letters, 2017, 645: 14-18.

DOI：10.1016/j.neulet.2017.02.069

• ACTH
• Memory consolidation
• Hippocampus
• Kcna1-null mice
• Nootropic effect
• Epilepsy

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.

• 出版日期2017-4-3