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Catecholaminergic neuronal network dysfunction in the frontal lobe of a genetic mouse model of schizophrenia

  • Shuji Iritani (a1), Hirotaka Sekiguchi (a1), Chikako Habuchi (a1), Youta Torii (a1), Keisuke Kuroda (a2), Kozo Kaibuchi (a2) and Norio Ozaki (a1)...



The precise aetiology of schizophrenia remains unclear. The neurodevelopmental hypothesis of schizophrenia has been proposed based on the accumulation of genomic or neuroimaging studies.


In this study, we examined the catecholaminergic neuronal networks in the frontal cortices of disrupted-in-schizophrenia 1 (DISC1) knockout (KO) mice, which are considered to be a useful model of schizophrenia.


Six DISC1 homozygous KO mice and six age-matched littermates were used. The animals’ brains were cut into 20-μm-thick slices, which were then immunohistochemically stained using an anti-tyrosine hydroxylase (TH) monoclonal antibody.


The TH-immunopositive fibres detected in the orbitofrontal cortices of the DISC1 KO mice were significantly shorter than those seen in the wild-type mice.


These neuropathological findings indicate that the hypofrontal symptoms of schizophrenia are associated with higher mental function deficiencies or cognitive dysfunction such as a loss of working memory.


Corresponding author

Shuji Iritani, Department of Psychiatry, Nagoya University Graduate School of Medicine, Tsurumai 65, Shouwa, Nagoya, Aichi 466-8550, Japan. Tel: +8 152 744 2282; Fax: +8 152 744 2293; E-mail:


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