Catecholaminergic neuronal network dysfunction in the frontal lobe of a genetic mouse model of schizophrenia.
BACKGROUND
The precise aetiology of schizophrenia remains unclear. The neurodevelopmental hypothesis of schizophrenia has been proposed based on the accumulation of genomic or neuroimaging studies.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
1Department of Psychiatry,Graduate School of Medicine,Nagoya University,Showa-ku,Nagoya,Aichi,Japan.
Shuji
S
Iritani
1Department of Psychiatry,Graduate School of Medicine,Nagoya University,Showa-ku,Nagoya,Aichi,Japan.
Hirotaka
H
Sekiguchi
1Department of Psychiatry,Graduate School of Medicine,Nagoya University,Showa-ku,Nagoya,Aichi,Japan.
Chikako
C
Habuchi
1Department of Psychiatry,Graduate School of Medicine,Nagoya University,Showa-ku,Nagoya,Aichi,Japan.
Youta
Y
Torii
2Department of Cell Pharmacology,Graduate School of Medicine,Nagoya University,Showa-ku,Nagoya,Aichi,Japan.
Keisuke
K
Kuroda
2Department of Cell Pharmacology,Graduate School of Medicine,Nagoya University,Showa-ku,Nagoya,Aichi,Japan.
Kozo
K
Kaibuchi
1Department of Psychiatry,Graduate School of Medicine,Nagoya University,Showa-ku,Nagoya,Aichi,Japan.
Norio
N
Ozaki
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase
DISC1; animal model; frontal lobe; schizophrenia; tyrosine hydroxylase