Antioxidant treatment alleviates cognitive deficits in a mouse model of schizophrenia

Schizophrenia is a devastating mental disorder with a complex symptomatology that among others comprises hallucinations and delusions (so-called positive symptoms), emotional blunting, poverty of speech, asociality and listlessness (negative symptoms) as well as cognitive dysfunctions. It is known from human genetic studies that, besides environmental factors, there is a strong genetic contribution to disease development. It may at first sight seem weird to study schizophrenia in mice, but mouse models are valuable tools to improve our knowledge for the disease. It is undoubted that we cannot study hallucinations or delusions in mice, but we can certainly get information about their emotional and cognitive state by using specific behavioral tests.

Interestingly, there is only one schizophrenia-associated locus that is not found in rodents: The human G72/G30 gene region. Therefore, David-M. Otte recently generated and characterized a mouse line in our laboratory by introducing the human G72/G30 locus into the mouse genome. These so-called transgenic mice in fact exhibited schizophrenia-like symptoms (Otte et al., 2009). In a follow-up study, David-M. Otte and his collaborators specifically addressed the cognitive impairment observed in the G72 animals. They revealed that the communication between neurons is disturbed, due to dysfunctions in the energy metabolism of the cells. Abnormalities in energy-producing mitochondria lead to oxidative stress, meaning that there is an overproduction of deleterious reactive oxygen species. The poor cognitive abilities of the G72 transgenic mice improved dramatically after feeding them with NAC (N-acetyl cysteine). NAC is a precursor of the tripeptide glutathione, which acts as an antioxidant by scavenging reactive oxygen species. Indeed, NAC treatment led to an increased cognitive performance in the transgenic mice, which suggests an option for the therapy of G72-associated psychiatric disorders like schizophrenia.

ORIGINAL RESEARCH PAPER

Otte DM, Sommersberg B, Kudin A, Guerrero C, Albayram O, Filiou MD, Frisch P, Yilmaz O, Drews E, Turck CW, Bilkei-Gorzó A, Kunz WS, Beck H, Zimmer A. N-acetyl Cysteine Treatment Rescues Cognitive Deficits Induced by Mitochondrial Dysfunction in G72/G30 Transgenic Mice. Neuropsychopharmacology. 2011 Jun 29. doi: 10.1038/npp.2011.109. [Epub ahead of print].

2011_Otte_Neuropsychopharmacol.pdf