Nature Neuroscience
- 9, 1382 - 1387 (2006)
Published online: 15 October 2006; | doi:10.1038/nn1791
2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP–dependent metabolic regulation of chromatin structureMireia Garriga-Canut1, 3, Barry Schoenike1, 3, Romena Qazi2, Karen Bergendahl1, Timothy J Daley1, Rebecca M Pfender1, John F Morrison1, Jeffrey Ockuly1, Carl Stafstrom1, Thomas Sutula1 & Avtar Roopra11
Department of Neurology, Medical Science Center, Room 1715, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706, USA. 2
Department of Pathology and Microbiology, The Aga Khan University, Karachi 74800, Pakistan. 3
These authors contributed equally to this work.
Correspondence should be addressed to Avtar Roopra roopra@neurology.wisc.edu 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.
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