Gene expressions in cerebral palsy subjects reveal structural and functional changes in the gastrocnemius muscle that are closely associated with passive muscle stiffness

AbstractCerebral palsy (CP) is a non-progressive motor disorder that affects posture and gait due to contracture development. The purpose of this study is to analyze a possible relation between muscle stiffness and gene expression levels in muscle tissue of children with CP. Next-generation sequencing (NGS) of gene transcripts was carried out in muscle biopsies from gastrocnemius muscle (n = 13 children with CP andn = 13 typical developed (TD) children). Passive stiffness of the ankle plantarflexors was measured. Structural changes of the basement membranes and the sarcomere length were measured. Twelve pre-defined gene target sub-categories of muscle function, structure and metabolism showed significant dif ferences between muscle tissue of CP and TD children. Passive stiffness was significantly correlated to gene expression levels of HSPG2 (p = 0.02;R2 = 0.67), PRELP (p = 0.002;R2 = 0.84), RYR3 (p = 0.04;R2 = 0.66), C COL5A3 (p = 0.0007;R2 = 0.88), ASPH (p = 0.002;R2 = 0.82) and COL4A6 (p = 0.03;R2 = 0.97). Morphological differences in the basement membrane were observed between children with CP and TD children. The sarcomere length was significantly increased in children with CP when compared with TD (p = 0.04). These findings show that gene targets in the categories: calcium handling, basement membrane and collagens, were significantly correlated to passive muscle stiffness. A Reactome pathway analysis showed that pathways involved in DNA rep...
Source: Cell and Tissue Research - Category: Cytology Source Type: research