| 研究課題/領域番号 |
23K09766
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分58040:法医学関連
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| 研究機関 | 香川大学 |
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研究代表者 |
モストファ ジャーマル 香川大学, 医学部, 助教 (50418802)
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| 研究期間 (年度) |
2023-04-01 – 2026-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2025年度: 390千円 (直接経費: 300千円、間接経費: 90千円)
2024年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2023年度: 2,860千円 (直接経費: 2,200千円、間接経費: 660千円)
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| キーワード | MPTP / COA-Cl / Nicotine / Ethanol / Striatum / ethanol / dopamine loss / MPTP-treated mice |
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| 研究開始時の研究の概要 |
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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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
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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| 今後の研究の推進方策 |
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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