title: Adrenocorticotropic hormone protects learning and memory function in epileptic Kcna1-null mice.
abstract: 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 7days - 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.
authors.affiliation: Department of Pediatrics, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Morris H
authors.initials: MH
authors.lastname: Scantlebury
authors.affiliation: Department of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph Hospital and Medical Center Phoenix, Arizona, USA; Department of Obstetrics and Gynecology, College of Medicine, Inje University, Ilsan-Paik Hospital, Gyeonggi, Republic of Korea.
authors.forename: Kyoung-Chul
authors.initials: KC
authors.lastname: Chun
authors.affiliation: Department of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph Hospital and Medical Center Phoenix, Arizona, USA.
authors.forename: Shun-Chieh
authors.initials: SC
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Clinical Neurosciences, Physiology and Pharmacology, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
authors.affiliation: Department of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph Hospital and Medical Center Phoenix, Arizona, USA. Electronic address: doyoung.kim@dignityhealth.org.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D019706:Excitatory Postsynaptic Potentials; D051662:Kv1.1 Potassium Channel / Q000235:genetics*; D007858:Learning / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: C496947:Kcna1 protein, mouse; D018696:Neuroprotective Agents; D051662:Kv1.1 Potassium Channel; D000324:Adrenocorticotropic Hormone
keywords: ACTH; Epilepsy; Hippocampus; Kcna1-null mice; Memory consolidation; Nootropic effect