期刊
NEUROPSYCHOPHARMACOLOGY
卷 36, 期 11, 页码 2233-2243出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2011.109
关键词
G72Tg mice exhibit altered mitochondrial activity and increased production of ROS; G72Tg mice show synaptic deficits and impaired spatial learning; NAC treatment completely restores spatial learning ability in G72Tg mice
资金
- Federal Ministry of Education and Research [NGFN2 01G10474, NGFN-MOODS FKZ 01GS08144, 01GW0511]
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. Neuropsychopharmacology (2011) 36, 2233-2243; doi: 10.1038/npp.2011.109; published online 29 June 2011
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