Anticonvulsant and proconvulsant actions of 2-deoxy-d-glucose

MacIej Gasior, Jessica Yankura, Adam L. Hartman, Amy French, Michael A Rogawski

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Purpose: 2-Deoxy-d-glucose (2-DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2-DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3-methyl-glucose (3-MG), which like 2-DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis. Methods: Mice were treated with 2-DG or 3-MG and the seizure threshold determined in the 6-Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. PTZ) or kainic acid (i.v. KA) seizure threshold tests. 2-DG was also tested in fully amygdala-kindled rats. Results: 2-DG (125-500 mgkg, i.p., 30 min before testing) significantly elevated the seizure threshold in the 6-Hz seizure test. 2-DG (250-500 mgkg) decreased the threshold in the MEST and i.v. PTZ and i.v. KA tests. 3-MG had no effect on seizure threshold in the 6-Hz test but, like 2-DG, decreased seizure threshold in the i.v. PTZ test. 2-DG (250 and 500 mgkg, i.p., 30 min before testing) had no effect on amygdala-kindled seizures. Conclusions: Although 2-DG protects against seizures in the 6-Hz seizure test, it promotes seizures in some other models. The proconvulsant action may relate to reduced glucose uptake, whereas the anticonvulsant action may require inhibition of glycolysis and shunting of glucose metabolism through the pentose phosphate pathway.

Original languageEnglish (US)
Pages (from-to)1385-1394
Number of pages10
JournalEpilepsia
Volume51
Issue number8
DOIs
StatePublished - 2010

Fingerprint

Anticonvulsants
Seizures
Glucose
Pentylenetetrazole
Electroshock
Glycolysis
Amygdala
Pentose Phosphate Pathway
Kainic Acid
Carbohydrate Metabolism

Keywords

  • 2-Deoxy-d-glucose
  • 3-Methyl-glucose
  • Glucose metabolism
  • Glycolysis
  • Ketogenic diet
  • Kindling
  • Pentose phosphate pathway

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

Anticonvulsant and proconvulsant actions of 2-deoxy-d-glucose. / Gasior, MacIej; Yankura, Jessica; Hartman, Adam L.; French, Amy; Rogawski, Michael A.

In: Epilepsia, Vol. 51, No. 8, 2010, p. 1385-1394.

Research output: Contribution to journalArticle

Gasior, M, Yankura, J, Hartman, AL, French, A & Rogawski, MA 2010, 'Anticonvulsant and proconvulsant actions of 2-deoxy-d-glucose', Epilepsia, vol. 51, no. 8, pp. 1385-1394. https://doi.org/10.1111/j.1528-1167.2010.02593.x
Gasior, MacIej ; Yankura, Jessica ; Hartman, Adam L. ; French, Amy ; Rogawski, Michael A. / Anticonvulsant and proconvulsant actions of 2-deoxy-d-glucose. In: Epilepsia. 2010 ; Vol. 51, No. 8. pp. 1385-1394.
@article{a1e955dac9814a3b90803b41c09991c5,
title = "Anticonvulsant and proconvulsant actions of 2-deoxy-d-glucose",
abstract = "Purpose: 2-Deoxy-d-glucose (2-DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2-DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3-methyl-glucose (3-MG), which like 2-DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis. Methods: Mice were treated with 2-DG or 3-MG and the seizure threshold determined in the 6-Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. PTZ) or kainic acid (i.v. KA) seizure threshold tests. 2-DG was also tested in fully amygdala-kindled rats. Results: 2-DG (125-500 mgkg, i.p., 30 min before testing) significantly elevated the seizure threshold in the 6-Hz seizure test. 2-DG (250-500 mgkg) decreased the threshold in the MEST and i.v. PTZ and i.v. KA tests. 3-MG had no effect on seizure threshold in the 6-Hz test but, like 2-DG, decreased seizure threshold in the i.v. PTZ test. 2-DG (250 and 500 mgkg, i.p., 30 min before testing) had no effect on amygdala-kindled seizures. Conclusions: Although 2-DG protects against seizures in the 6-Hz seizure test, it promotes seizures in some other models. The proconvulsant action may relate to reduced glucose uptake, whereas the anticonvulsant action may require inhibition of glycolysis and shunting of glucose metabolism through the pentose phosphate pathway.",
keywords = "2-Deoxy-d-glucose, 3-Methyl-glucose, Glucose metabolism, Glycolysis, Ketogenic diet, Kindling, Pentose phosphate pathway",
author = "MacIej Gasior and Jessica Yankura and Hartman, {Adam L.} and Amy French and Rogawski, {Michael A}",
year = "2010",
doi = "10.1111/j.1528-1167.2010.02593.x",
language = "English (US)",
volume = "51",
pages = "1385--1394",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Anticonvulsant and proconvulsant actions of 2-deoxy-d-glucose

AU - Gasior, MacIej

AU - Yankura, Jessica

AU - Hartman, Adam L.

AU - French, Amy

AU - Rogawski, Michael A

PY - 2010

Y1 - 2010

N2 - Purpose: 2-Deoxy-d-glucose (2-DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2-DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3-methyl-glucose (3-MG), which like 2-DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis. Methods: Mice were treated with 2-DG or 3-MG and the seizure threshold determined in the 6-Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. PTZ) or kainic acid (i.v. KA) seizure threshold tests. 2-DG was also tested in fully amygdala-kindled rats. Results: 2-DG (125-500 mgkg, i.p., 30 min before testing) significantly elevated the seizure threshold in the 6-Hz seizure test. 2-DG (250-500 mgkg) decreased the threshold in the MEST and i.v. PTZ and i.v. KA tests. 3-MG had no effect on seizure threshold in the 6-Hz test but, like 2-DG, decreased seizure threshold in the i.v. PTZ test. 2-DG (250 and 500 mgkg, i.p., 30 min before testing) had no effect on amygdala-kindled seizures. Conclusions: Although 2-DG protects against seizures in the 6-Hz seizure test, it promotes seizures in some other models. The proconvulsant action may relate to reduced glucose uptake, whereas the anticonvulsant action may require inhibition of glycolysis and shunting of glucose metabolism through the pentose phosphate pathway.

AB - Purpose: 2-Deoxy-d-glucose (2-DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2-DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3-methyl-glucose (3-MG), which like 2-DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis. Methods: Mice were treated with 2-DG or 3-MG and the seizure threshold determined in the 6-Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. PTZ) or kainic acid (i.v. KA) seizure threshold tests. 2-DG was also tested in fully amygdala-kindled rats. Results: 2-DG (125-500 mgkg, i.p., 30 min before testing) significantly elevated the seizure threshold in the 6-Hz seizure test. 2-DG (250-500 mgkg) decreased the threshold in the MEST and i.v. PTZ and i.v. KA tests. 3-MG had no effect on seizure threshold in the 6-Hz test but, like 2-DG, decreased seizure threshold in the i.v. PTZ test. 2-DG (250 and 500 mgkg, i.p., 30 min before testing) had no effect on amygdala-kindled seizures. Conclusions: Although 2-DG protects against seizures in the 6-Hz seizure test, it promotes seizures in some other models. The proconvulsant action may relate to reduced glucose uptake, whereas the anticonvulsant action may require inhibition of glycolysis and shunting of glucose metabolism through the pentose phosphate pathway.

KW - 2-Deoxy-d-glucose

KW - 3-Methyl-glucose

KW - Glucose metabolism

KW - Glycolysis

KW - Ketogenic diet

KW - Kindling

KW - Pentose phosphate pathway

UR - http://www.scopus.com/inward/record.url?scp=77955340185&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955340185&partnerID=8YFLogxK

U2 - 10.1111/j.1528-1167.2010.02593.x

DO - 10.1111/j.1528-1167.2010.02593.x

M3 - Article

C2 - 20491877

AN - SCOPUS:77955340185

VL - 51

SP - 1385

EP - 1394

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 8

ER -