Deficiency in short-chain fatty acid beta-oxidation affects theta oscillations during sleep

Nat Genet. 2003 Jul;34(3):320-5. doi: 10.1038/ng1174.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcarnitine / administration & dosage
  • Acyl-CoA Dehydrogenase
  • Animals
  • Brain / enzymology*
  • Disease Models, Animal
  • Electroencephalography
  • Fatty Acid Desaturases / deficiency*
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism
  • Fatty Acids / metabolism*
  • Immunoblotting
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Lactoylglutathione Lyase / metabolism
  • Liver / enzymology
  • Male
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Nootropic Agents / administration & dosage
  • Oligonucleotide Array Sequence Analysis
  • Oxidation-Reduction
  • Sleep, REM* / drug effects
  • Theta Rhythm*


  • Fatty Acids
  • Nootropic Agents
  • Acetylcarnitine
  • Fatty Acid Desaturases
  • Acyl-CoA Dehydrogenase
  • Lactoylglutathione Lyase

Associated data

  • GENBANK/AK005055
  • GENBANK/BC019817
  • GENBANK/BC027063
  • GENBANK/L11163