Diacylglycerol kinase epsilon modulates rapid kindling epileptogenesis.

摘要: Summary: Purpose: Diacylglycerol kinase epsilon (DGKe) regulates seizure susceptibility and long-term potentiation through arachidonoyl-inositol lipid signaling. We studied the significance of arachidonoyl-diacylglycerol (20:4 DAG) in epileptogenesis DGKe-deficient mice undergoing rapid kindling epileptogenesis. Methods: Tripolar electrode units were implanted right dorsal hippocampi male DGKe+/+ DGKe−/− mice. Ten days after surgery, was achieved by stimulating 6 times daily for 4 with a subconvulsive electrical stimulation (10-s train 50-Hz biphasic pulses, 75–200 μA amplitude) at 30-min intervals. After 1 week, rekindled. EEGs recorded analyzed to characterize epileptogenic events as spikes, sharp waves, or abnormal amplitudes rhythms. Right histology [Timm's staining, neuropeptide Y (NPY) glial fibrillary acidic protein immunoreactivity], DNA fragmentation (TUNEL). Results: had significantly fewer motor epileptic compared from second day stimulation. These differences maintained during rekindling. also exhibited low-amplitude spike–wave complexes, short spreading depression, predominant lower-frequency (1–4 Hz) bands throughout stimulation, whereas increased high-frequency (4–8 Hz; 8–15 determined power spectral analysis. displayed no sprouting supragranular area NPY inmunoreactivity hilus weak astrocyte reactivation all hippocampal areas. No TUNEL-positive cells detected any group mice. Conclusions: DGKe modulates inositol Because arachidonate-containing diacylglycerol phosphorylation phosphatidic acid is selectively blocked mice, we postulate that shortage arachidonoyl-moiety lipids and/or messengers derived thereof key signaling event epileptogenesis.