Project/Area Number |
12680740
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Nerve anatomy/Neuropathology
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Research Institution | Yokohama City University School of Medicine (2002) Shiga University of Medical Science (2000-2001) |
Principal Investigator |
NISHIMURA Akiyoshi Yokohama City University School of Medicine, Legal Medicine, Associate Professor, 医学部, 助教授 (60283561)
|
Co-Investigator(Kenkyū-buntansha) |
SAWADA Masato Fujita Health University Institute for Comprehensive Medical Science, Joint research Division for Therapies against Intractable Diseases, Professor, 総合医科学研究所, 教授 (10187297)
OZAKI Norio Fujita Health University School of Medicine, Psychiatry, Professor, 医学部, 教授 (40281480)
IKEMOTO Keiko National Minami Hanamaki Hospital, Clinical Research Institute, Chief, 臨床研究部, 生化学研究室長 (90184449)
NISHI Katsuji Shiga University Medical Science, Legal Medicine, Professor, 医学部, 教授 (60073681)
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Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | sepiapterin reductase / immunohistochemistry / tyrosine hydroxylase / tetrahydrobiopterin / monoamine / nucleus accumbency / aromatic L-amino acid decarboxylase / schizophrenia / immunohistochemistry / モノアミン / 精神分裂病 / セロトニン2Aレセプター / チロシン水酸化酵素 / 芳香族アミノ酸脱炭酸酵素 |
Research Abstract |
In this study, we found many Aromatic L-amino acid decarboxylase positive, tyrosine hydroxylase negative and tryptophan hydroxylase negative neurons (D-neurons) in the nucleus (Acc) of human. The number of D-neurons in schizophrenic patients was significantly lower than in controls (p<0.05, t-test) in the Acc. And, we found the spherical deposits (SPDs) with a size of 3-10μ in diameter mainly within the inner and middle molecular layer of the dentate gyrus of hippocampal formation by lectin staining. The number of the SPDs in schizophrenic patients was higher than in aged individuals and degenerative dementia patients. The Acc receives fiber projections of excitatory amino acid from the hippocampus, anterior cingulate cortex, amygdala and thalamus, and the nucleus projects to ventral palladium and midbrain. The Acc is thought to be an interface that converts emotion to action and to relate to the etiology of schizophrenia. The perforate pathway synapses on the outer portion of the dentate that arises from the dentate gyrus granule cells. This subtends approximately two-thirds of the granule cell dendrites and the perforate pathway contributes 80-85% of the synaptic terminals that end in this zone. By contrast, the inner one-third portion of the molecular layer receives afferents from the CA4 zone and from the septum. The presence of many SPDs in the molecular layer of the dentate gyrus suggests that there may exist a disadvantageous interaction between these deposits and dendrites of neurons of the CA4 zone of the hippocampus and may play a key part in the perturbation of the memory of patients with schizophrenia and/or degenerative dementias. Concerning the hippocampal formation, hypotheses of a possible hippocampal etiology of schizophrenia have been formulated. This study suggests that D-neurons in the Acc and SPDs in the dentate gyrus of hippocampal formation may relate to the pathology of schizophrenia.
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