title: Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP-induced mouse model of Parkinson's disease.
abstract: The canonical Wnt signaling pathway is critical for the development of midbrain dopaminergic (DA) neurons, and recent studies have suggested that disruption of this signaling cascade may underlie the pathogenesis of Parkinson's disease (PD). However, the exact role of the canonical Wnt signaling pathway, including low-density lipoprotein receptor-related protein 5 and 6 (LRP5/6) and β-catenin components, in a mouse model of PD remains unclear. In the present study, the tyrosine hydroxylase (TH)-Cre transgenic mouse line was used to generate mice with the specific knockout of LRP5, LRP6 or β-catenin in DA neurons. Following inactivation of LRP5, LRP6 or β-catenin, TH-immunohistochemical staining was performed. The results indicated that β-catenin is required for the development or maintenance of these neurons; however, LRP5 and LRP6 were found to be dispensable. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, the depletion of LRP5, LRP6 or β-catenin was found to be protective for the midbrain DA neurons to a certain extent. Thesein vivoresults provide a novel perspective for the function of the canonical Wnt signaling pathway in a mouse model of PD.
authors.affiliation: Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Ting-Li
authors.initials: TL
authors.lastname: Dai
authors.affiliation: Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Chan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Xue-Yuan
authors.initials: XY
authors.lastname: Niu
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China ; Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hu
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China ; Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China ; Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China ; Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China ; Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China ; Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China ; Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Yu-Qiang
authors.initials: YQ
authors.lastname: Ding
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China ; Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Song
authors.affiliation: Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Liao
keywords: LRP5; LRP6; MPTP; Parkinson’s disease; dopaminergic neuron; β-catenin