Wnt signaling pathway is involved in the pathogenesis of amyotrophic lateral sclerosis in adult transgenic mice
Authors: Chen, Yanchun; Guan, Yingjun; Zhang, Zhenghou; Liu, Huancai; Wang, Shanshan; Yu, Li; Wu, Xin; Wang, Xin
Source: Neurological Research, Volume 34, Number 4, May 2012 , pp. 390-399(10)
Publisher: Maney Publishing
Abstract:Objective: Our aim was to examine the change in expression of molecules involved in Wnt signaling in the pathogenesis of amyotrophic lateral sclerosis (ALS) in adult transgenic mice, and to reveal the relationship between the Wnt signaling pathway and the pathogenesis of ALS.
Methods: We determined the expression of Wnt2, Wnt7a, and GSK-3beta in the spinal cord of SOD1G93A ALS transgenic mice at different ages using reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry. Using double labeling, we determined whether Wnt2, Wnt7a, and GSK-3beta were colocalized with beta-tubulin III, for neurons, or glial fibrillary acidic protein, for mature astrocytes.
Results: Wnt2, Wnt7a mRNA and protein in the spinal cord of ALS mice were upregulated and compared with wild-type mice. Phospho-GSK-3beta (Ser 9) protein levels in the spinal cord of ALS mice were upregulated. Moreover, the immunoreactivity of Wnt2, Wnt7a, and phospho-GSK-3beta (Ser 9) was strong in ALS mice but weak in wild-type mice at the same time points. Double immunofluorescence labeling showed that Wnt2 and Wnt7a were expressed in both neurons and astrocytes, whereas GSK-3beta was expressed only in neurons. Most of the double positive cells were located in the ventral horns of the gray matter, the locus of neurodegeneration.
Discussion: Neurodegeneration upregulated the expression of Wnt2 and Wnt7a in the spinal cord of ALS mice, which in turn activated Wnt signaling, and accordingly inhibited GSK-3beta activity in disease progression of ALS in adult transgenic mice; this could regulate the downstream gene of the Wnt signaling pathway and promote cell proliferation.
Document Type: Original Article
Affiliations: Shandong University School of Medicine, Jinan, China
Publication date: 2012-05-01
- Authors wishing to cite fast track papers should give the journal name and the article DOI. This will enable reference linking via CrossRef and allow forward and backward citation tracking systems to associate the fast track citation with the final journal reference.
- Editorial Board
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Information for Advertisers
- Terms & Conditions
- Virtual Maney - Stroke
- Top articles
- Health Sciences Spotlight
- ingentaconnect is not responsible for the content or availability of external websites