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Brain Res. 2017 Jan 1;1654(Pt A):66-76. doi: 10.1016/j.brainres.2016.10.011. Epub 2016 Oct 17.

Late treatment with choline alfoscerate (l-alpha glycerylphosphorylcholine, α-GPC) increases hippocampal neurogenesis and provides protection against seizure-induced neuronal death and cognitive impairment.

Author information

1
Department of Neurology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
2
Department of Physiology, Hallym University, College of Medicine, Chuncheon, Republic of Korea.
3
Inha University, Department of Nursing, Incheon, Republic of Korea.
4
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.
5
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.

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.

KEYWORDS:

Blood brain barrier; Choline alfoscerate; Cognitive impairment; Epilepsy; Neuron death; Pilocarpine

PMID:
27765578
DOI:
10.1016/j.brainres.2016.10.011
[Indexed for MEDLINE]

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