Deficiency in short-chain fatty acid beta-oxidation affects theta oscillations during sleep |
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Authors: | Tafti Mehdi Petit Brice Chollet Didier Neidhart Elisabeth de Bilbao Fabienne Kiss Jozsef Z Wood Philip A Franken Paul |
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Institution: | Biochemistry and Genetics Unit, Department of Psychiatry, University of Geneva and Geneva University Hospitals, Chemin du Petit-Bel-Air 2, 1225 Chêne-Bourg, Switzerland. mehdi.tafti@medecine.unige.ch |
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Abstract: | In rodents, the electroencephalogram (EEG) during paradoxical sleep and exploratory behavior is characterized by theta oscillations. Here we show that a deficiency in short-chain acyl-coenzyme A dehydrogenase (encoded by Acads) in mice causes a marked slowing in theta frequency during paradoxical sleep only. We found Acads expression in brain regions involved in theta generation, notably the hippocampus. Microarray analysis of gene expression in mice with mutations in Acads indicates overexpression of Glo1 (encoding glyoxylase 1), a gene involved in the detoxification of metabolic by-products. Administration of acetyl-L-carnitine (ALCAR) to mutant mice significantly recovers slow theta and Glo1 overexpression. Thus, an underappreciated metabolic pathway involving fatty acid beta-oxidation also regulates theta oscillations during sleep. |
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