Purines and neuronal excitability: Links to the ketogenic diet

S. A. Masino, M. Kawamura, D. N. Ruskin, J. D. Geiger, D. Boison

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalEpilepsy Research
Volume100
Issue number3
DOIs
StatePublished - Jul 1 2012

Fingerprint

Ketogenic Diet
Purines
Anticonvulsants
Adenosine
Seizures
Adenosine Triphosphate
Diet Therapy
Adenosine A1 Receptors
Neurons
Research
Transgenic Mice
Epilepsy
Diet

Keywords

  • ATP
  • Adenosine
  • Epilepsy
  • Hemichannel
  • Hippocampus
  • Long-term potentiation
  • Metabolism
  • Seizure
  • Transgenic mouse

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Purines and neuronal excitability : Links to the ketogenic diet. / Masino, S. A.; Kawamura, M.; Ruskin, D. N.; Geiger, J. D.; Boison, D.

In: Epilepsy Research, Vol. 100, No. 3, 01.07.2012, p. 229-238.

Research output: Contribution to journalArticle

Masino, S. A. ; Kawamura, M. ; Ruskin, D. N. ; Geiger, J. D. ; Boison, D. / Purines and neuronal excitability : Links to the ketogenic diet. In: Epilepsy Research. 2012 ; Vol. 100, No. 3. pp. 229-238.
@article{99fccd96828e45d5bd799c0b170137c8,
title = "Purines and neuronal excitability: Links to the ketogenic diet",
abstract = "ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms.",
keywords = "ATP, Adenosine, Epilepsy, Hemichannel, Hippocampus, Long-term potentiation, Metabolism, Seizure, Transgenic mouse",
author = "Masino, {S. A.} and M. Kawamura and Ruskin, {D. N.} and Geiger, {J. D.} and D. Boison",
year = "2012",
month = "7",
day = "1",
doi = "10.1016/j.eplepsyres.2011.07.014",
language = "English (US)",
volume = "100",
pages = "229--238",
journal = "Epilepsy Research",
issn = "0920-1211",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Purines and neuronal excitability

T2 - Links to the ketogenic diet

AU - Masino, S. A.

AU - Kawamura, M.

AU - Ruskin, D. N.

AU - Geiger, J. D.

AU - Boison, D.

PY - 2012/7/1

Y1 - 2012/7/1

N2 - ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms.

AB - ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms.

KW - ATP

KW - Adenosine

KW - Epilepsy

KW - Hemichannel

KW - Hippocampus

KW - Long-term potentiation

KW - Metabolism

KW - Seizure

KW - Transgenic mouse

UR - http://www.scopus.com/inward/record.url?scp=84864083358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864083358&partnerID=8YFLogxK

U2 - 10.1016/j.eplepsyres.2011.07.014

DO - 10.1016/j.eplepsyres.2011.07.014

M3 - Article

C2 - 21880467

AN - SCOPUS:84864083358

VL - 100

SP - 229

EP - 238

JO - Epilepsy Research

JF - Epilepsy Research

SN - 0920-1211

IS - 3

ER -