Early Gene Expression Changes in Skeletal Muscle from SOD1(G93A) Amyotrophic Lateral Sclerosis Animal Model

Author(s)

de Oliveira, Gabriela P. ^[1] ; Maximino, Jessica R. ^[1] ; Maschietto, Mariana ^[2] ; Zanoteli, Edmar ^[1] ; Puga, Renato D. ^[3] ; Lima, Leandro ^[2] ; Carraro, Dirce M. ^[2] ; Chadi, Gerson ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Dept Neurol, Neuroregenerat Ctr, BR-01246903 Sao Paulo - Brazil

^[2] AC Camargo Hosp, Lab Genom & Mol Biol CIPE, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Inst Psychiat, BR-01246903 Sao Paulo - Brazil

• Document type: Journal article
• Source: Cellular and Molecular Neurobiology; v. 34, n. 3, p. 451-462, APR 2014.
• Web of Science Citations: 13

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of motor neurons. Familial ALS is strongly associated to dominant mutations in the gene for Cu/Zn superoxide dismutase (SOD1). Recent evidences point to skeletal muscle as a primary target in the ALS mouse model. Wnt/PI3 K signaling pathways and epithelial-mesenchymal transition (EMT) have important roles in maintenance and repair of skeletal muscle. Wnt/PI3 K pathways and EMT gene expression profile were investigated in gastrocnemius muscle from SOD1(G93A) mouse model and age-paired wild-type control in the presymptomatic ages of 40 and 80 days aiming the early neuromuscular abnormalities that precede motor neuron death in ALS. A customized cDNA microarray platform containing 326 genes of Wnt/PI3 K and EMT was used and results revealed eight up-regulated (Loxl2, Pik4ca, Fzd9, Cul1, Ctnnd1, Snf1lk, Prkx, Dner) and nine down-regulated (Pik3c2a, Ripk4, Id2, C1qdc1, Eif2ak2, Rac3, Cds1, Inppl1, Tbl1x) genes at 40 days, and also one up-regulated (Pik3ca) and five down-regulated (Cd44, Eef2 k, Fzd2, Crebbp, Piki3r1) genes at 80 days. Also, protein-protein interaction networks grown from the differentially expressed genes of 40 and 80 days old mice have identified Grb2 and Src genes in both presymptomatic ages, thus playing a potential central role in the disease mechanisms. mRNA and protein levels for Grb2 and Src were found to be increased in 80 days old ALS mice. Gene expression changes in the skeletal muscle of transgenic ALS mice at presymptomatic periods of disease gave further evidence of early neuromuscular abnormalities that precede motor neuron death. The results were discussed in terms of initial triggering for neuronal degeneration and muscle adaptation to keep function before the onset of symptoms. (AU)

• FAPESP's process: 10/20457-7 - Characterization of the role of Schwann cells on the neurodegeneration events of motoneurons in the animal model an in the patients with the amyotrophic lateral sclerosis
• Grantee: Gerson Chadi
• Support Opportunities: Regular Research Grants