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 language | English (US) |
|---|---|
| Pages (from-to) | 1385-1394 |
| Number of pages | 10 |
| Journal | Epilepsia |
| Volume | 51 |
| Issue number | 8 |
| DOIs | |
| State | Published - 2010 |
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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 journal › Article
}
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 -