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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Dysregulated expression of death, stress and mitochondrion related genes in the sciatic nerve of presymptomatic SOD1(G93A) mouse model of Amyotrophic Lateral Sclerosis

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Author(s):
Alves, Chrystian J. [1] ; Maximino, Jessica R. [1] ; Chadi, Gerson [1]
Total Authors: 3
Affiliation:
[1] Univ Sao Paulo, Sch Med, Neuroregenerat Ctr, Dept Neurol, BR-01246903 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: FRONTIERS IN CELLULAR NEUROSCIENCE; v. 9, SEP 1 2015.
Web of Science Citations: 25
Abstract

Schwann cells are the main source of paracrine support to motor neurons. Oxidative stress and mitochondrial dysfunction have been correlated to motor neuron death in Amyotrophic Lateral Sclerosis (ALS). Despite the involvement of Schwann cells in early neuromuscular disruption in ALS, detailed molecular events of a dying-back triggering are unknown. Sciatic nerves of presymptomatic (60-day-old) SOD1(G93A) mice were submitted to a high-density oligonucleotide microarray analysis. DAVID demonstrated the deregulated genes related to death, stress and mitochondrion, which allowed the identification of Cell cycle, ErbB signaling, Tryptophan metabolism and Rig-l-like receptor signaling as the most representative KEGG pathways. The protein-protein interaction networks based upon deregulated genes have identified the top hubs (TRAF2, H2AFX, E2F1, FOXO3, MSH2, NGFR, TGFBR1) and bottlenecks (TRAF2, E2F1, CDKN1B, TWIST1, FOXO3). Schwann cells were enriched from the sciatic nerve of presymptomatic mice using flow cytometry cell sorting. qPCR showed the up regulated (Ngfr, Cdnkn1b, E2f1, Traf2 and Erbb3, H2afic, Cdkn1a, Hspa1, Prdx, Mapk10) and down-regulated (Foxo3, Mtor) genes in the enriched Schwann cells. In conclusion, molecular analyses in the presymptomatic sciatic nerve demonstrated the involvement of death, oxidative stress, and mitochondrial pathways in the Schwann cell non-autonomous mechanisms in the early stages of ALS. (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