2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure

Mireia Garriga-Canut, Barry Schoenike, Romena Qazi, Karen Bergendahl, Timothy J. Daley, Rebecca M. Pfender, John F. Morrison, Jeffrey Ockuly, Carl Stafstrom, Thomas Sutula, Avtar Roopra

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1382-1387
Number of pages6
JournalNature neuroscience
Volume9
Issue number11
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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