| Project/Area Number |
19K10687
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 58040:Forensics medicine-related
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
塚本 郁子 香川大学, 医学部, 寄附講座教員 (10183477)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Ethanol / nicotine / dopamine / ethanol / Dopamine / tyrosine hydroxylase / MPTP-treated mice / MPTP / dopamine metaboliies / TH phosphorylation / mouse brain / Nicotine / MPP+ / PC12 / Mortality / Monoamines / MPP / cell culture / cell viability / dopaminergic neuron / Parkinson's model |
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| Outline of Research at the Start |
We will use toxin-induced mouse and cellular models of PD for the first time to test both the individual and combined effects of nicotine, EtOH and/or ACE on protection against dopaminergic neuron injuries.
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| Outline of Final Research Achievements |
EtOH (2.0 and 3.0 g/kg) alone reversed the effects of MPTP treatment in both studied brain regions, as evidenced by an increase in DA, DOPAC, and HVA levels, TH expression, and Ser31 phosphorylation compared to the control, indicating restorative effects on striatal and hippocampal DA neurons in the MPTP model. Likewise, NIC (1.0 and 2.0 mg/kg) alone reversed MPTP treatment effects, with treated mice showing increased DA, DOPAC, and HVA contents, TH expression, and Ser31 phosphorylation compared to control mice. Co-administration of EtOH (2.0 g/kg) and NIC (1.0 mg/kg) further increased DA and HVA tissue contents, TH expression, and Ser31 phosphorylation, indicating an additive effect.
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| Academic Significance and Societal Importance of the Research Achievements |
Our results show that EtOH and NIC induce similar increases in brain DA and TH via TH phosphorylation activation in MPTP model mice. EtOH and NIC showed an additive effect in combination, suggesting that their co-application could be a potent therapeutic strategy for treating PD.
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