title: Late treatment with choline alfoscerate (l-alpha glycerylphosphorylcholine, α-GPC) increases hippocampal neurogenesis and provides protection against seizure-induced neuronal death and cognitive impairment.
abstract: Choline alfoscerate (α-GPC) is a common choline compound and acetylcholine precursor in the brain, which has been shown to be effective in the treatment of Alzheimer's disease and dementia. α-GPC has been shown to enhance memory and cognitive function in stroke and Alzheimer's patients but currently remains untested in patients suffering from epilepsy. This study aimed to evaluate whether α-GPC treatment after seizure can ameliorate seizure-induced cognitive impairment and neuronal injury. The potential therapeutic effects of α-GPC on seizure-induced cognitive impairment were tested in an animal model of pilocarpine-induced seizure. Seizures were induced by intraperitoneal injection of pilocarpine (25mg/kg) in male rats. α-GPC (250mg/kg) was injected into the intramuscular space once daily for one or three weeks from immediately after seizure, or from 3 weeks after the seizure onset for 3 weeks. Here we found that immediate 1-week treatment of α-GPC showed no neuroprotective effects and neurogenesis. Immediate 3-week treatment of α-GPC showed neuroprotective effect but no effect on neurogenesis. To evaluate the effect of late treatment of α-GPC on cognitive impairment following seizure, rats were injected α-GPC from 3 weeks after seizure for 3 weeks and subjected to a water maze test. In the present study, we found that administration of α-GPC starting at 3 weeks after seizure improved cognitive function through reduced neuronal death and BBB disruption, and increased neurogenesis. Therefore, α-GPC injection may serve as a beneficial treatment for improvement of cognitive function in epilepsy patients.
authors.affiliation: Department of Neurology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Song Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: A Ra
authors.initials: AR
authors.lastname: Kho
authors.affiliation: Inha University, Department of Nursing, Incheon, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Department of Neurology, Hallym University, College of Medicine, Chuncheon, Republic of Korea; Hallym Institute of Epilepsy Research, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Hong Ki
authors.initials: HK
authors.lastname: Song
authors.affiliation: Department of Neurology, Hallym University, College of Medicine, Chuncheon, Republic of Korea; Hallym Institute of Epilepsy Research, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Hui Chul
authors.initials: HC
authors.lastname: Choi
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea; Hallym Institute of Epilepsy Research, Hallym University, College of Medicine, Chuncheon, Republic of Korea. Electronic address: swsuh@hallym.ac.kr.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005997:Glycerylphosphorylcholine / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010862:Pilocarpine; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D010862:Pilocarpine; D005997:Glycerylphosphorylcholine; D002795:Choline O-Acetyltransferase
keywords: Blood brain barrier; Choline alfoscerate; Cognitive impairment; Epilepsy; Neuron death; Pilocarpine