TY - JOUR
T1 - Electrical control in neurons by the ketogenic diet
AU - Sada, Nagisa
AU - Inoue, Tsuyoshi
N1 - Funding Information:
NS is a research fellow of the Japan Society for the Promotion of Science, JSPS. This work was supported in part by Grant-in-Aid for Scientific Research (15K07966 and 18H02719 to TI) and Grant-in-Aid for JSPS Research Fellow (17J09536 to NS) from JSPS, the translational research program TR-SPRINT from the Japan Agency for Medical Research and Development, AMED (JP18lm0203019 to TI), and research grants from Takeda Science Foundation and Hoansha Foundation (to TI).
PY - 2018/7/16
Y1 - 2018/7/16
N2 - The ketogenic diet is used as a diet treatment for drug-resistant epilepsy, but there are no antiepileptic drugs based on the ketogenic diet. The ketogenic diet changes energy metabolites (ketone bodies, glucose and lactate) in the brain, which consequently changes electrical activities in neurons and ultimately suppresses seizures in epileptic patients. In order to elucidate the antiseizure effects of the ketogenic diet, it is important to clarify the mechanism by which these metabolic changes are converted to electrical changes in neurons. In this review, we summarize electrophysiological studies focusing on electrical control in neurons by the ketogenic diet. Recent studies have identified electrical regulators driven by the ketogenic diet: ion channels (ATP-sensitive K+ channels and voltage-dependent Ca2+ channels), synaptic receptors (AMPA-type glutamate receptors and adenosine A1 receptors), neurotransmitter transporters (vesicular glutamate transporters), and others (BCL-2- associated agonist of cell death and lactate dehydrogenase). Thus, the ketogenic diet presumably elicits neuronal inhibition via the combined actions of these molecules. From the viewpoint of drug development, these molecules are valuable as targets for the development of new antiepileptic drugs. Drug therapy to mimic the ketogenic diet may be feasible in the future, through the combination of multiple antiepileptic drugs targeting these molecules.
AB - The ketogenic diet is used as a diet treatment for drug-resistant epilepsy, but there are no antiepileptic drugs based on the ketogenic diet. The ketogenic diet changes energy metabolites (ketone bodies, glucose and lactate) in the brain, which consequently changes electrical activities in neurons and ultimately suppresses seizures in epileptic patients. In order to elucidate the antiseizure effects of the ketogenic diet, it is important to clarify the mechanism by which these metabolic changes are converted to electrical changes in neurons. In this review, we summarize electrophysiological studies focusing on electrical control in neurons by the ketogenic diet. Recent studies have identified electrical regulators driven by the ketogenic diet: ion channels (ATP-sensitive K+ channels and voltage-dependent Ca2+ channels), synaptic receptors (AMPA-type glutamate receptors and adenosine A1 receptors), neurotransmitter transporters (vesicular glutamate transporters), and others (BCL-2- associated agonist of cell death and lactate dehydrogenase). Thus, the ketogenic diet presumably elicits neuronal inhibition via the combined actions of these molecules. From the viewpoint of drug development, these molecules are valuable as targets for the development of new antiepileptic drugs. Drug therapy to mimic the ketogenic diet may be feasible in the future, through the combination of multiple antiepileptic drugs targeting these molecules.
KW - Antiepileptic drug
KW - Electrophysiology
KW - Epilepsy
KW - Glucose
KW - Ketogenic diet
KW - Ketone body
KW - Lactate
UR - http://www.scopus.com/inward/record.url?scp=85053407004&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053407004&partnerID=8YFLogxK
U2 - 10.3389/fncel.2018.00208
DO - 10.3389/fncel.2018.00208
M3 - Short survey
AN - SCOPUS:85053407004
VL - 12
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
SN - 1662-5102
M1 - 208
ER -