Orexin B protects dopaminergic neurons from 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity associated with reduced extracellular signal-regulated kinase phosphorylation.

Autor: Ma X; Institute of Mental Health, Jining Medical University, Jining, Shandong, 272067, China., Cao F; Institute of Mental Health, Jining Medical University, Jining, Shandong, 272067, China.; Xiamen Key Laboratory of Translational Medical of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, Xiamen, 361000, China., Cui J; Institute of Mental Health, Jining Medical University, Jining, Shandong, 272067, China., Li X; Institute of Mental Health, Jining Medical University, Jining, Shandong, 272067, China., Yin Z; Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China., Wu Y; Institute of Mental Health, Jining Medical University, Jining, Shandong, 272067, China. wuyili@wmu.edu.cn.; Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. wuyili@wmu.edu.cn., Wang Q; Institute of Mental Health, Jining Medical University, Jining, Shandong, 272067, China. qqwang@mail.jnmc.edu.cn.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2024 May 24; Vol. 51 (1), pp. 669. Date of Electronic Publication: 2024 May 24.
DOI: 10.1007/s11033-024-09587-2
Abstrakt: Background: The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) is a major pathological hallmark of Parkinson's disease (PD). Orexin B (OXB) has been reported to promote the growth of DA neurons. However, the roles of OXB in the degeneration of DA neurons still remained not fully clear.
Methods: An in vivo PD model was constructed by administrating 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Pole test was performed to investigate the motor function of mice and the number of DA neurons was detected by immunofluorescence (IF). A PD cell model was established by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+). OXB was added to the culture medium 2 h after MPP + treatment. Microscopic analysis was carried out to investigate the function of OXB in the cell model of PD 24 h after MPP + challenge. RNA-Seq analysis of the PD cell model was performed to explore the possible mechanisms. Western blot was used to detect the phosphorylation levels of extracellular signal-regulated kinase (ERK).
Results: OXB significantly decreased the DA neurons death caused by MPTP, alleviated MPP+-induced neurotoxicity in SH-SY5Y cells, and robustly enhanced the weight and motor ability of PD mice. Besides, RNA-Seq analysis demonstrated that the mitogen-activated protein kinase (MAPK) pathway was involved in the pathology of PD. Furthermore, MPP + led to increased levels of phosphorylation of ERK (p-ERK), OXB treatment significantly decreased the levels of p-ERK in MPP+-treated SH-SY5Y cells.
Conclusions: This study demonstrated that OXB exerts a neuroprotective role associated with reduced ERK phosphorylation in the PD model. This suggests that OXB may have therapeutic potential for treatment of PD.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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