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

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


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.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Cell Death / drug effects
  • Choline O-Acetyltransferase / metabolism
  • Cognition / drug effects
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / prevention & control*
  • Disease Models, Animal
  • Glycerylphosphorylcholine / administration & dosage*
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Male
  • Maze Learning / drug effects
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / pathology
  • Neural Stem Cells / physiology
  • Neurogenesis / drug effects
  • Neurons / drug effects*
  • Neurons / pathology
  • Neurons / physiology
  • Neuroprotective Agents / administration & dosage*
  • Pilocarpine
  • Rats, Sprague-Dawley
  • Seizures / complications
  • Seizures / drug therapy*
  • Seizures / pathology
  • Seizures / physiopathology


  • Neuroprotective Agents
  • Pilocarpine
  • Glycerylphosphorylcholine
  • Choline O-Acetyltransferase