Impairment of the tyrosine hydroxylase neuronal network in the orbitofrontal cortex of a genetically modified mouse model of schizophrenia

Important genes have been identified that are associated with susceptibility to schizophrenia. DISC1 is one of these candidate genes. The protein 14-3-3 epsilon is a DISC1-interacting molecule and is associated with axon elongation. The genetically modified 14-3-3 epsilon heterozygous knockout mice are considered to be an animal model of schizophrenia because they present endophenotypes of schizophrenia including working memory impairment. This study investigated the immunohistochemical expression of tyrosine hydroxylase (TH) to reveal the alterations in the functional structure of the axon elongation caused by the deficit of 14-3-3 epsilon. The study focused on the orbitofrontal cortex in the prefrontal cortex which is a region of interest in schizophrenia research. The investigation used eight 15-week-old knockout mice and six age-matched wild-type mice. The TH immunopositive fibers were linear and dense in the wild-type mice. These fibers were serpentine, thin and short in the knockout mice. Although it appeared that dendritic spine-like immunopositive varices were strung tightly in the fibers of wild-type mice, these were few and sparse in those of the of the knockout mice. Quantitative analysis showed a significant decrease in the total extent of the TH-immunopositive fibers in the orbital cortex of the knockout mouse. There is thought to be a dysfunction of a neurotransmitter such as dopamine and noradrenalin in the prefrontal cortex of these knockout mice.

Research highlights► Impairment of the orbitofrontal cortex of a 14-3-3 epsilon heterozygous knockout mouse. ► Immunohistochemical approach to reveal the alterations in the functional structure. ► A significant decrease of tyrosine hydroxylase immunopositive fibers in this area. ► Few and sparse dendritic spine-like varices of tyrosine hydroxylase immunopositive fibers.