| Project/Area Number |
16591162
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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 | NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY |
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Principal Investigator |
YAMADA Mitsuhiko NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY, DIVISION OF PSYCHOGERIATRICS, DIRECTOR, 精神保健研究所・老人精神保健部, 部長 (60240040)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIJIMA Kunotoshi SHOWA UNIV., DEPT PSYCHIATRY, PROFESSOR, 医学部, 教授 (80051613)
OHATA Hisayuki SHOWA UNIV., DEPT PHARMACOLOGY, ASSISTANT PROFESSOR, 薬学部, 助教授 (00119166)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | ANTIDEPRESSANT / PRESYNAPSE / NEUROTRANSMITTER / EXOCYTOSIS / SYNAPTIC VESICLE / うつ病 / タンパク |
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| Research Abstract |
The biological basis for the therapeutic mechanisms of depression are still unknown. We have previously performed EST analysis and identified some common biological changes induced after chronic antidepressant treatment as antidepressant related genes/ESTs : ADRG#1-707. Then, we developed our original cDNA microarray on which ADRG#1-707 were spotted, for rapid secondary screening of candidate genes as the novel therapeutic targets. With this microarray, we found that the expression of some of the ADRGs were related to neurotransmiter release and located on synaptic vesicle. Indeeed, VAMP2/synaptobrevin, cysteine string protein, synapsin I, Rab-1A and Rab-3B were induced after chronic sertraline treatment in rat frontal cortex. Western blot analysis also demonstrated the induction of these ADRGs at protein levels after chronic treatment with imipramine and sertraline. In addition, synaptophysin and secretogranin II, often used as a marker protein for small synaptic vesicle or large dense core granule were significantly increased after chronically treatment with antidepressants. On the other hand, the expression of SNAP-25 and syntaxin-1, which are used as markers for synapse and make a SNARE-complex with VAMP2, were not affected by these treatments. These results suggested that the number of synaptic vesicles, but not the number of synapses, was increased after chronic antidepressant treatment. The synaptic vesicles and proteins may be a new target molecular system for antidepressant.
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