| 研究実績の概要 |
We examined the effect of EtOH on MPTP-induced reduction of DA content and the expression of tyrosine hydroxylase (TH) and its phosphorylation at Ser31 in the striatum of both wild type (WT) and Aldh2-knockout (Aldh2-KO) mice. MPTP-treated mice, which are used as a Parkinson’s disease (PD) model, were treated with the saline control or EtOH (1.0-3.0 g/kg, i.p.) and brain samples were collected 1 h after saline or EtOH administration. DA and its metabolites were measured by HPLC-ECD, while TH expression and Ser31 phosphorylation were analyzed by western blot. Results show that MPTP treatment significantly decreased the concentration of DA and its metabolites DOPAC and HVA, accompanied by a decrease in Ser31 phosphorylation and TH expression compared to the vehicle (MPTP-free) in both genotypes. However, EtOH (2.0 and 3.0 g/kg) reversed the effects of MPTP treatment, as evidenced by an increase in DA, DOPAC, and HVA levels compared to the saline control in both WT and Aldh2-Ko mice. In addition, EtOH-treated (2.0 and 3.0 g/kg) mice showed higher levels of Ser31 phosphorylation and TH expression. The EtOH-induced DA response was blunted in Aldh2-KO mice compared to WT mice, suggesting that acetaldehyde may exert an opposite effect. These findings suggest that TH is activated via phosphorylation to increase DA metabolism during EtOH exposure in mice. Our data imply that a moderate-high dose of EtOH can protect against the striatal DA loss induced by MPTP in mice and support the use of EtOH as a neuroprotective agent for PD.
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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
Due to the construction of animal facility which began in May 2020, the experiment was delayed in commencing in time. In April 2021, I began to use MPTP to induce mouse models of PD followed by drug treatment. HPLC-ECD analysis of dopamine and its metabolites are almost finished. Now, I prepare to analyze the samples using Western blot.
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