| Project/Area Number |
08671123
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Department of Mental Disorder Research, National Institute of Neuroscience, NCNP |
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Principal Investigator |
TAKAHASHI Katsunobu National Institute of Neuroscience, NCNP Department of Mental Disorder Reaserch, Section Chief, 神経研究所・疾病研究第3部, 室長 (40183850)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Toru National Institute of Neuroscience, NCNP Department of Mental Disorder Reaserch,, 神経センター・精神研究所・疾病研究第3部, 部長 (00198441)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Cyclic ADP-ribose / Brain / DC38 / Neuropsychiatric disease / 環状ADPリボース |
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| Research Abstract |
Cyclic adenosine diphosphoribose (cyclic ADP-ribose), a metabolite of beta-NAD<@D1+@>D1, was first discovered in sea urchin eggs by Lee and his colleagues as a novel intracellular messenger with Ca<@D12+@>D1-imbilizing activity. It is expected that the cyclic nucleotide mediates Ca<@D12+@>D1release from an inositol 1,4,5-triphosphate-insensitive Ca<@D12+@>D1 store. The cyclic ADP-ribose-synthesizing enzyme, termed ADP-ribosyl cyclase, is especially abundant in Aplysia ovotestis, from which it was purified as a 29 kDa cytoplasmic protein and sequenced. Interestingly, the ADP-ribosyl cyclase has an amino acid sequence homologous to that of human CD38 antigen which is a 46-kDa type II glycoprotein with a single-transmembrane domain. To investigate cyclic ADP-ribose in mammalian brain, we developed radioimmunoassay for the cyclic nucleotide, and obtained the follwing findings.1. Content of cyclic ADFP-ribose in brain (163(]SY.+-。[)9 pmol/g tissue) was the highest amoung rat tissues tested. No correlation of the content and CD38 expression in tissues was observed. 2. The investigation of anatomical distribution of cyclic ADP-ribose in rat brain revealed that the cyclic nucleotide was abundant in all regions of brain tissue (150-250 pmol/g tissue). 3. Cyclic ADP-ribose in rat cerebral cortex was localized mainly in synapostsomal fraction (47% of total) and cytosolic fracion (39%). 4. High contents of cyclic ADP-ribose were detected in frontal cortex (498(]SY.+-。[)59 pmol/g tissue) and parietal cortex (591(]SY.+-。[)92 pmol/g tissue) of human post-mortam brains, which wer 3-4 times higher than that of rat cerebral cortex. 5. There were no sttistically significant difference between the cyclic ADP-ribose contetns in the parietal cortex of controls and those of patients with schizoprenia, dementia of the Alzheimer type or vasclular dementia.
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