Back to Search
Start Over
2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure.
- Source :
-
Nature neuroscience [Nat Neurosci] 2006 Nov; Vol. 9 (11), pp. 1382-7. Date of Electronic Publication: 2006 Oct 15. - Publication Year :
- 2006
-
Abstract
- Temporal lobe epilepsy is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in the rat kindling model of temporal lobe epilepsy. We show that 2DG potently reduces the progression of kindling and blocks seizure-induced increases in the expression of brain-derived neurotrophic factor and its receptor, TrkB. This reduced expression is mediated by the transcription factor NRSF, which recruits the NADH-binding co-repressor CtBP to generate a repressive chromatin environment around the BDNF promoter. Our results show that 2DG has anticonvulsant and antiepileptic properties, suggesting that anti-glycolytic compounds may represent a new class of drugs for treating epilepsy. The metabolic regulation of neuronal genes by CtBP will open avenues of therapy for neurological disorders and cancer.
- Subjects :
- Alcohol Oxidoreductases genetics
Animals
Chromatin drug effects
DNA-Binding Proteins genetics
Diet
Disease Progression
Down-Regulation drug effects
Energy Metabolism physiology
Epilepsy diet therapy
Gene Expression drug effects
Glycolysis drug effects
Glycolysis physiology
Hippocampus drug effects
Hippocampus metabolism
Kindling, Neurologic physiology
NAD physiology
Neuronal Plasticity drug effects
Rats
Receptor, trkB biosynthesis
Receptor, trkB genetics
Repressor Proteins genetics
Transcription Factors genetics
Alcohol Oxidoreductases physiology
Antimetabolites pharmacology
Chromatin physiology
DNA-Binding Proteins physiology
Deoxyglucose pharmacology
Epilepsy drug therapy
Epilepsy metabolism
Repressor Proteins physiology
Transcription Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6256
- Volume :
- 9
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Nature neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 17041593
- Full Text :
- https://doi.org/10.1038/nn1791