sphingosine-phosphorylcholine and Seizures

1. Excessive excitation of brain neurons by the excitatory neurotransmitter, glutamate, induces a cascade of events leading to increased intracellular Ca++, neuronal degeneration and death. 2. Recent in vitro research has demonstrated that a natural cationic amphiphile in the brain, lysosphingomyelin, may be able to prevent neuronal degeneration by repressing phosphosinositidase-C overactivation induced by excessive excitation of the metabotropic glutamate receptor. 3. This research tested the latter finding in vivo in a rat model of glutamate excitotoxicity. Intracerebroventricular (i.c.v.) administration of the Group 1 metabotropic glutamate receptor (mGluR) agonist, quisqualate, produced seizures, akinesia, destruction of hippocampal pyramidal cell dendritic microtubule-associated protein-2, and major loss of hippocampal CA sector neurons. 4. Prophylactic i.c.v. infusion of lysosphingomyelin powerfully attenuates these quisqualate-induced behaviors and prevents neuronal degeneration. 5. Lysosphingomyelin may be of clinical use in allaying progressive Group 1 mGluR-induced hippocampal cognitive and motor disorders including Alzheimer's disease, brain seizure, and stroke.

Topics: Animals; Behavior, Animal; Dyskinesia, Drug-Induced; Excitatory Amino Acid Agonists; Hippocampus; Immunohistochemistry; Injections, Intraventricular; Lateral Ventricles; Male; Microtubule-Associated Proteins; Neurons; Phosphorylcholine; Quisqualic Acid; Rats; Rats, Inbred F344; Receptors, Metabotropic Glutamate; Seizures; Sphingosine