Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP‑induced mouse model of Parkinson's disease

Dai,Ting‑Li; Zhang,Chan; Peng,Fang; Niu,Xue‑Yuan; Hu,Ling; Zhang,Qiong; Huang,Ying; Chen,Ling; Zhang,Lei; Zhu,Weidong; Ding,Yu‑Qiang; Song,Ning‑Ning; Liao,Min

doi:10.3892/etm.2014.1745

Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP‑induced mouse model of Parkinson's disease

Authors:
- Ting‑Li Dai
- Chan Zhang
- Fang Peng
- Xue‑Yuan Niu
- Ling Hu
- Qiong Zhang
- Ying Huang
- Ling Chen
- Lei Zhang
- Weidong Zhu
- Yu‑Qiang Ding
- Ning‑Ning Song
- Min Liao
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Affiliations: Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China, 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
Published online on: May 28, 2014 https://doi.org/10.3892/etm.2014.1745
Pages: 384-390

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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. These in vivo results provide a novel perspective for the function of the canonical Wnt signaling pathway in a mouse model of PD.

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