Increased ratio of calcineurin immunoreactive neurons in the caudate nucleus of patients with schizophrenia |
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Authors: | Wada Akira Kunii Yasuto Ikemoto Keiko Yang Qiaohui Hino Mizuki Matsumoto Junya Niwa Shin-ichi |
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Affiliation: | Departments of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan. |
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Abstract: | Calcineurin (CaN) has been investigated extensively in numerous biochemical, behavioral, and genetic studies in schizophrenia because its function is closely related to dopamine-glutamate signal transduction, which is thought to be associated with pathophysiological changes in schizophrenia. Although evidence has suggested that dysfunction of CaN may be a risk factor for schizophrenia, there have been few reports focusing on the expression of CaN mRNA and CaN protein levels in the brains of schizophrenic patients. In addition, findings on CaN expression in postmortem brains from patients with schizophrenia have been inconsistent. Here, we conducted immunohistochemical examinations of several regions in postmortem brains, including the dorsolateral prefrontal cortex (DLPFC), hippocampus, caudate nucleus, and putamen, using specific antibodies, and compared the results from the brains of nine schizophrenic subjects to nine age- and sex-matched control subjects. There was no significant difference in the ratio of CaN immunoreactive (IR) neurons between schizophrenia and control groups in the DLPFC or hippocampus, and a significantly increased ratio of CaN-IR neurons was seen in the caudate nucleus in the brains from schizophrenia patients. As the striatum contains most of the brain dopamine, the results of the present study have critical implications and suggest that alterations in CaN signaling in the caudate contribute to the pathogenesis of schizophrenia. This is the first report of caudate CaN abnormalities in schizophrenia. |
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Keywords: | AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate BA46, Brodmann's Area 46 BDNF, brain neurotrophic factor CaN, Calcineurin DAB, diaminobenzidine DG, dentate gyrus DARPP-32, dopamine- and cAMP-regulated phosphoprotein of molecular weight 32,000 DLPFC, dorsolateral prefrontal cortex DOI, duration of illness IR, immunoreactive GABA, γ-aminobutyric acid NMDA, N-methyl-d-aspartate NMDAR, NMDA receptors PBS, phosphate buffered saline PCP, phencyclidine PET, positron emission tomography PMI, postmortem interval |
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