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Analysis of the neuromuscular signaling pathway and its interaction with the Muscular Atrophy pathway in an experimental model of Knee Osteoarthritis

Grant number: 17/24192-7
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): April 01, 2018
Effective date (End): March 31, 2020
Field of knowledge:Health Sciences - Physiotherapy and Occupational Therapy
Principal researcher:Tania de Fatima Salvini
Grantee:Jonathan Emanuel da Cunha
Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Osteoarthritis is a degenerative disease involving joints and periarticular tissues in which the knee is the most affected joint. Knee Osteoarthritis (KOA) is characterized by inflammatory mediators increase, joint-space narrowing, osteophytes formation, pain and swelling. However, there is no scientific evidence on neuromuscular signaling pathways related to changes in KOA. The study hypothesis is that the muscular impairments in KOA are associated with changes in the neuromuscular junction. Aim: to identify the neuromuscular signaling database and the morphological structure of the neuromuscular junction in KOA in rats. Possible correlations as pathways of Muscular Atrophy were also analyzed. Methods: adult male rats (Wistar) will be randomly allocated into 2 groups (n = 20/group): control (no intervention); KOA (ACLT knee surgery). After 60 days, the animals will be evaluated morphology end plate and gene expression in muscle. The expression of genes linked to neuromuscular signaling (IL-6, TNF-±, Atrogin 1, MuRF-1, NFK², IGF-1, mTOR, MyoD, Myostatin, Dok-7, Lrp4, ²-AChR, ´-AChR and N CAM) of the quadriceps and tibialis anterior muscles. As well as the morphology of JNM, with confocal laser scanning microscopy will be analyzed. The results will be distributed regarding normality and homogeneity. The statistical difference between groups will be assessed by using Student T Test or Mann-Whitney. In conclusion, the findings of this study may provide new scientific evidence about the changes at the neuromuscular signaling pathways in KOA. (AU)

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