TY - JOUR

T1 - Reduced mitochondrial DNA and OXPHOS protein content in skeletal muscle of children with cerebral palsy

AU - von Walden, Ferdinand

AU - Vechetti, Ivan J.

AU - Englund, Davis

AU - Figueiredo, Vandre C.

AU - Fernandez-Gonzalo, Rodrigo

AU - Murach, Kevin

AU - Pingel, Jessica

AU - Mccarthy, John J.

AU - Stal, Per

AU - Ponten, Eva

PY - 2021

Y1 - 2021

N2 - 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%; pINTERPRETATION 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.

AB - 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%; pINTERPRETATION 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.

KW - YOUNG-PEOPLE

KW - EXERCISE

KW - CAPACITY

KW - ADULTS

KW - EXPRESSION

KW - RESISTANCE

KW - MODELS

U2 - 10.1111/dmcn.14964

DO - 10.1111/dmcn.14964

M3 - Journal article

C2 - 34176131

VL - 63

SP - 1204

EP - 1212

JO - Developmental medicine and child neurology. Supplement

JF - Developmental medicine and child neurology. Supplement

SN - 0419-0238

IS - 10

ER -