| Project/Area Number |
23K09766
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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 |
モストファ ジャーマル 香川大学, 医学部, 助教 (50418802)
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| Project Period (FY) |
2023-04-01 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | MPTP / COA-Cl / Nicotine / Ethanol / Striatum / ethanol / dopamine loss / MPTP-treated mice |
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| Outline of Research at the Start |
Nicotine and ethanol (EtOH) are often consumed together and produce an additive increase in dopamine release in the nucleus accumbens. COA-Cl has recently been shown to increase dopamine levels and to exert neuroprotective effects both in vivo and in vitro.
Thus, the present study is aimed to investigate whether a combination of COA-Cl, EtOH and/or nicotine exerts additive neuroprotective effects against MPTP-induced neurotoxicity, and to identify its underlying mechanisms, with a focus on apoptosis.
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| Outline of Annual Research Achievements |
Previously, local perfusion of COA-Cl (0.05-1.0 mM) produced a significant and dose-dependent increase in dopamine (DA) levels, with the highest dose of 1.0 mM COA-Cl producing an approximately 5-fold increase in DA. Additionally, we showed that COA-Cl significantly enhanced DA release by 3.0 to 5.0-fold, accompanied by an increase in tyrosine hydroxylase at Ser31 and Ser40.
Here, we utilized 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models of Parkinson’s disease to explore whether COA-Cl could reverse the loss of DA caused by MPTP in the dorsal striatum. Preliminary data revealed that COA-Cl restored DA levels, suggesting its potential restorative effects on DA depletion in mouse striatum.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
We aim to examine the effects of COA-Cl (0.05, 0.1, or 4.0 mM) combined with nicotine and/or ethanol on extracellular levels of DA and tyrosine hydroxylase phosphorylation in the dorsal striatum of MPTP-induced mouse model of PD. The rationale for this study is to investigate the role of COA-Cl alone or in combination with nicotine or ethanol in restoring dopamine function in the brain.
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| Strategy for Future Research Activity |
These studies are currently underway to explore the potential synergistic effects of combining COA-Cl with nicotine and or ethanol in restoring DA function in mouse models of PD.
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