N-acetyl cysteine treatment rescues cognitive deficits induced by mitochondrial dysfunction in G72/G30 transgenic mice

Neuropsychopharmacology. 2011 Oct;36(11):2233-43. doi: 10.1038/npp.2011.109. Epub 2011 Jun 29.


Genetic studies have implicated the evolutionary novel, anthropoid primate-specific gene locus G72/G30 in psychiatric diseases. This gene encodes the protein LG72 that has been discussed to function as a putative activator of the peroxisomal enzyme D-amino-acid-oxidase (DAO) and as a mitochondrial protein. We recently generated 'humanized' bacterial artificial chromosome transgenic mice (G72Tg) expressing G72 transcripts in cells throughout the brain. These mice exhibit several behavioral phenotypes related to psychiatric diseases. Here we show that G72Tg mice have a reduced activity of mitochondrial complex I, with a concomitantly increased production of reactive oxygen species. Affected neurons display deficits in short-term plasticity and an impaired capability to sustain synaptic activity. These deficits lead to an impairment in spatial memory, which can be rescued by pharmacological treatment with the glutathione precursor N-acetyl cysteine. Our results implicate LG72-induced mitochondrial and synaptic defects as a possible pathomechanism of psychiatric disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Animals
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / enzymology
  • Cognition Disorders / genetics
  • Electron Transport Complex I / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Mice, Transgenic
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology
  • Reactive Oxygen Species / metabolism
  • Treatment Outcome


  • Carrier Proteins
  • DAOA protein, human
  • Intracellular Signaling Peptides and Proteins
  • Reactive Oxygen Species
  • Electron Transport Complex I
  • Acetylcysteine