Wnt signaling pathway is involved in the pathogenesis of amyotrophic lateral sclerosis in adult transgenic mice.
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 SOD1(G93A) 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.


CONCLUSIONS
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.
Department of Histology and Embryology, Shandong University School of Medicine, Jinan, China.
Yanchun
Y
Chen
Yingjun
Y
Guan
Zhenghou
Z
Zhang
Huancai
H
Liu
Shanshan
S
Wang
Li
L
Yu
Xin
X
Wu
Xin
X
Wang
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D018450:Disease Progression; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
D051153:Wnt Proteins