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Reduced mitochondrial DNA and OXPHOS protein content in skeletal muscle of children with cerebral palsy
Author(s) -
von Walden Ferdinand,
Vechetti Ivan J,
Englund Davis,
Figueiredo Vandré C,
FernandezGonzalo Rodrigo,
Murach Kevin,
Pingel Jessica,
Mccarthy John J,
Stål Per,
Pontén Eva
Publication year - 2021
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/dmcn.14964
Subject(s) - mitochondrial biogenesis , mitochondrial dna , skeletal muscle , biology , mitochondrion , respiratory chain , gene expression , endocrinology , medicine , oxidative phosphorylation , gene , microbiology and biotechnology , genetics , biochemistry
Aim To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP). Method Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9–18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7–21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were analyzed with a focused query investigating metabolism‐ and mitochondria‐related gene networks. Results The mtDNA to genomic DNA ratio was lower in the children with CP compared to the typically developing group (−23%, p =0.002). Out of five investigated complexes in the mitochondrial respiratory chain, we observed lower protein levels of all complexes (I, III, IV, V, −20% to −37%; p <0.05) except complex II. Total peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1α) messenger RNA ( p <0.004), isoforms PGC1α1 ( p =0.05), and PGC1α4 ( p <0.001) were reduced in CP. Transcriptional similarities were observed between CP, aging, and 90 days’ bed rest. Interpretation Mitochondrial biogenesis, mtDNA, and oxidative phosphorylation protein content are reduced in CP muscle compared with typically developing muscle. Transcriptional pathways shared between aging and long‐term unloading suggests metabolic dysregulation in CP, which may guide therapeutic strategies for combatting CP muscle pathology.What this paper adds Cerebral palsy (CP) muscle contains fewer energy‐generating organelles than typically developing muscle. Gene expression in CP muscle is similar to aging and long‐term bed rest.