title: Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy.
abstract: Epilepsy is a heterogeneous family of neurological disorders that manifest as seizures, i.e. the hypersynchronous activity of large population of neurons. About 30% of epileptic patients do not respond to currently available antiepileptic drugs. Decades of intense research have elucidated the involvement of a number of possible signaling pathways, however, at present we do not have a fundamental understanding of epileptogenesis. In this paper, we review the literature on epilepsy under a wide-angle perspective, a mandatory choice that responds to the recurrent and unanswered question about what is epiphenomenal and what is causal to the disease. While focusing on the involvement of K+ and glutamate/GABA in determining neuronal hyperexcitability, emphasis is given to astrocytic contribution to epileptogenesis, and especially to loss-of-function of astrocytic glutamine synthetase following reactive astrogliosis, a hallmark of epileptic syndromes. We finally introduce the potential involvement of abnormal glycogen synthesis induced by excess glutamate in increasing susceptibility to seizures.
authors.affiliation: MARBILab, Museo storico della fisica e Centro di studi e ricerche "Enrico Fermi", Rome, Italy. Electronic address: mauro.dinuzzo@neuroenergetics.org.
authors.forename: Mauro
authors.initials: M
authors.lastname: DiNuzzo
authors.affiliation: Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mangia
authors.affiliation: Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy; Fondazione Santa Lucia IRCCS, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Maraviglia
authors.affiliation: MARBILab, Museo storico della fisica e Centro di studi e ricerche "Enrico Fermi", Rome, Italy; Dipartimento di Fisica, Sapienza Università di Roma, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Giove
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D004827:Epilepsy / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006003:Glycogen; D011188:Potassium
keywords: Epilepsy; GABA; Glutamate; Glycogen; Potassium