25 April 2020 : Animal Research
A Mouse Model of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Induced Parkinson Disease Shows that 2-Aminoquinoline Targets JNK Phosphorylation
Meie Zhu1BCDEF, Daokai Gong1ABCDEF*DOI: 10.12659/MSM.920989
Med Sci Monit 2020; 26:e920989
Abstract
BACKGROUND: The pathological features of Parkinson disease (PD) include motor deficits, glial cell activation, and neuroinflammation. The neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has an oxidation product, 1-methyl-4-phenylpyridinium ion (MPP+). This study aimed to investigate the effects of 2-aminoquinoline on motor deficits in a mouse model of MPTP-induced PD and cultured mouse astrocytes treated with MPP+, to determine the effects on astrocyte proliferation and apoptosis.
MATERIAL AND METHODS: Motor deficits in the mouse model of MPTP-induced PD were investigated using the climbing time, suspension time, and swim time tests. Cultured mouse astrocytes were treated with MPP+, and mice with MPTP-induced PD were treated with increasing doses of 2-aminoquinoline. The MTT assay was used to measure astrocyte viability. Astrocyte apoptosis was assessed by confocal fluorescence microscopy using Annexin‑V and fluorescein isothiocyanate (FITC) staining. Western blot measured the levels of Bax, p‑JNK, Bcl‑2, and caspase‑3.
RESULTS: In the mouse model of MPTP-induced PD, motor deficit tests showed that 2-aminoquinoline reduced the impaired motor function during the climbing time, the suspension time, and the swim time tests in a dose-dependent manner. Pre-treatment with 2-aminoquinoline significantly reduced the proliferation and apoptosis of astrocytes induced by MPP+ in vitro, in a dose-dependent manner (P<0.05). The levels of p‑JNK and cleaved caspase‑3 levels were significantly reduced in astrocytes treated with MPP+ following pre-treatment with 2-aminoquinoline, which also reversed the increase in the Bax/Bcl‑2 ratio.
CONCLUSIONS: In the mouse model of MPTP-induced PD, 2-aminoquinoline reduced motor deficiencies, inhibited MPP+ activated astrocyte apoptosis, and regulated the Bax/Bcl-2 ratio by targeting p-JNK.
Keywords: Anti-Inflammatory Agents, Astrocytes, Neuroglia, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Aminoquinolines, dopaminergic neurons, JNK Mitogen-Activated Protein Kinases, Phosphorylation, Pyrrolidines
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