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.
[Show abstract][Hide abstract] ABSTRACT: Studies that seek to determine the etiology of schizophrenia through pathological images and morphological abnormalities of the brain have been conducted since the era of E. Kraepelin, and pioneers in neuropathology such as A. Alzheimer have also eagerly pursued such studies. However, there have been no disease-specific findings, and there was a brief era in which it was said that "schizophrenia is the graveyard of neuropathologists." However, since the 1980s, neuroimaging studies with CT and MRI etc., have been used in many reports of cases of schizophrenia with abnormal brain morphology, thus generating renewed interest in developments within brain tissue and leading to new neuropathological studies. There are now many reports in which, in addition to morphological observations, cell distribution and the like are image-processed and statistically processed through computers. Due to methodological problems in making progress in the field of cerebral pathology, we have not yet been able to observe disease-specific findings, although there are several findings with high certainty. However, the neurodevelopmental hypothesis has been supported as being able to reasonably explain the accumulated findings of previous studies. At the same time, results of recent molecular-biological studies have revealed the risk genes for this disease, and because many of those genes are associated with functions related to nerve differentiation, development, and plasticity, there is growing interest in their correlations with cerebral pathology. We are now on the verge of uncovering the etiology of this disease by integrating cerebral neuroimaging, molecular genetics, and cerebral neuropathology. In that sense, neuropathological studies of this disease from new viewpoints have become essential.
Nagoya journal of medical science 02/2013; 75(1-2):11-28. · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The importance of YWHAE gene polymorphisms (rs1532976, rs3752826, and rs9393) in the development of suicidal behavior has been studied in ethnic groups of Russians and Tatars from the Republic of Bashkortostan. It was revealed that the carriers of the YWHAE*C allele of rs3752826 polymorphism of the YWHAE gene have increased the risk of suicidal behavior (OR = 1.91), regardless of their ethnicity. In addition, the YWHAE*T allele of rs9393 polymorphism (OR = 2.21), YWHAE*T/*T genotype (OR = 2.73), and YWHAE*T allele (OR = 1.52) of the rs1532976 polymorphism, as well as the YWHAE*A*T haplotype of rs1532976 and rs9393 polymorphisms (OR = 1.54) represent genetic markers of the risk of suicidal behavior in the sample of subjects of Russian ethnicity.
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