Background: Choline alfoscerate (α-GPC) and Cytidine 5'-diphosphocholine (CDPCholine)
are both acetylcholine precursors and are considered to act as pro-cholinergic nootropic
agents. Acetylcholine precursors have also recently found frequent use in the neurology clinic.
Stroke and many types of dementia have been shown to respond favorably after treatment with
these agents, not only in terms of cognitive dysfunction but also behavioral and psychological
symptoms. The primary mechanisms of Acetylcholine precursors are the following: 1) Acetylcholine
precursors themselves are used in the biosynthesis of acetylcholine and 2) byproducts
like glycerophosphate have protective functions for neuronal phospholipids. However, whether
acetylcholine precursors have a similar effect in treating cognitive impairment in patients with
epilepsy remains controversial.
Methods: Our previous studies investigating acetylcholine precursors in seizure-experienced
animals have produced variable results that were dependent on the timing of administration.
Results: Early administration of CDP-choline immediately after seizure increased neuronal death,
blood-brain barrier (BBB) disruption and microglial activation in the hippocampus. However,
administration of α-GPC starting 3 weeks after seizure (late administration) improved cognitive
function through reduced neuronal death and BBB disruption, and increased neurogenesis in the
Conclusion: These seemingly contradictory results may be attributed to both epileptogenic features
and neuroprotective functions of several acetylcholine precursors.