title: The epsilon theory: a novel synthesis of the underlying molecular and electrophysiological mechanisms of primary generalized epilepsy and the possible mechanism of action of valproate.
abstract: Primary generalized epilepsy may be the result of maldevelopment of central nervous system and each seizure may be the consequence of a neuronal maladaptation to an unknown stimulus using the paleospinothalamical tract due to an overexpression of brain-derived neurotrophic factor and neurotrophin-3. The subsequent protein kinase C epsilon (PKC-epsilon) activation and intracellular Ca(2+) release causes a nociceptive hypersensitization and an increased cortical hyperexcitability because of increased frequency of synchronous Ca(2+) oscillations, cortical maldevelopment at the level of synapses and an attenuation of GABA(A) receptor mediated responses in reticular thalamic nucleus. Valproate may exert its antiepileptic effect as a PKC-epsilon inhibitor, and using with a PKC-epsilon activator that cannot pass blood brain barrier, its side effects may become avoidable.
authors.affiliation: Centre for Postgraduate Education, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary. toth_martin@yahoo.com
authors.forename: Marton
authors.initials: M
authors.lastname: Toth
mesh_terms: D002118:Calcium / Q000378:metabolism; D002490:Central Nervous System / Q000503:physiopathology*; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051744:Protein Kinase C-epsilon; D014635:Valproic Acid / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D009414:Nerve Growth Factors; D014635:Valproic Acid; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D002118:Calcium