Abstract
Down’s syndrome (DS) is a developmental disorder associated with intellectual disability (ID). We have previously shown that people with DS engage in very low levels of exercise compared to people with ID not due to DS. Many aspects of the DS phenotype, such as dementia, low activity levels and poor muscle tone, are shared with disorders of mitochondrial origin, and mitochondrial dysfunction has been demonstrated in cultured DS tissue. We undertook a phosphorus magnetic resonance spectroscopy (31P-MRS) study in the quadriceps muscle of 14 people with DS and 11 non-DS ID controls to investigate the post-exercise resynthesis kinetics of phosphocreatine (PCr), which relies on mitochondrial respiratory function and yields a measure of muscle mitochondrial function in vivo. We found that the PCr recovery rate constant was significantly decreased in adults with DS compared to non-DS ID controls (1.7±0.1 min−1 vs 2.1±0.1 min−1 respectively) who were matched for physical activity levels, indicating that muscle mitochondrial function in vivo is impaired in DS. This is the first study to investigate mitochondrial function in vivo in DS using 31P-MRS. Our study is consistent with previous in vitro studies, supporting a theory of a global mitochondrial defect in DS.
Highlights
Down’s syndrome (DS) is a developmental disorder associated with triplication of chromosome 21, and affects 1 in 700–1000 live births [1,2]
We undertook a study of DS mitochondrial function in vivo in skeletal muscle using 31P magnetic resonance spectroscopy (31P-MRS), which offers a non-invasive method for measuring mitochondrial function in vivo by analysing the post-exercise recovery kinetics of phosphocreatine (PCr), a process which relies on mitochondrial production of adenosine triphosphate (ATP) [9]
Four participants with DS were eliminated from the calculation of k due to not meeting the signal-to-noise ratio (SNR) requirements described in the Methods section, and the 31P-MRS and accelerometry results in Table 2 represent the DS group with n = 10
Summary
Down’s syndrome (DS) is a developmental disorder associated with triplication of chromosome 21, and affects 1 in 700–1000 live births [1,2]. We have recently reported reduced physical activity levels in DS compared to people with intellectual disability (ID) not due to DS, with the older people with DS being less active than their younger counterparts [5]. As this use of an ID control group eliminates a number of general (social and environmental) factors that might explain this observation, we postulated an underlying age-related pathophysiology which limits activity in people with DS, an obvious candidate for which is mitochondrial dysfunction [5]. We postulated that participants with DS would demonstrate a slowed recovery of PCr, indicating a defect of mitochondrial function in vivo, compared to control participants with similar levels of ID but not due to DS
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