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PloS One 2019Sarcopenia due to loss of skeletal muscle mass and strength leads to physical inactivity and decreased quality of life. The number of individuals with sarcopenia is...
Sarcopenia due to loss of skeletal muscle mass and strength leads to physical inactivity and decreased quality of life. The number of individuals with sarcopenia is rapidly increasing as the number of older people increases worldwide, making this condition a medical and social problem. Some patients with sarcopenia exhibit accumulation of peri-muscular adipose tissue (PMAT) as ectopic fat deposition surrounding atrophied muscle. However, an association of PMAT with muscle atrophy has not been demonstrated. Here, we show that PMAT is associated with muscle atrophy in aged mice and that atrophy severity increases in parallel with cumulative doses of PMAT. We observed severe muscle atrophy in two different obese model mice harboring significant PMAT relative to respective control non-obese mice. We also report that denervation-induced muscle atrophy was accelerated in non-obese young mice transplanted around skeletal muscle with obese adipose tissue relative to controls transplanted with non-obese adipose tissue. Notably, transplantation of obese adipose tissue into peri-muscular regions increased nuclear translocation of FoxO transcription factors and upregulated expression FoxO targets associated with proteolysis (Atrogin1 and MuRF1) and cellular senescence (p19 and p21) in muscle. Conversely, in obese mice, PMAT removal attenuated denervation-induced muscle atrophy and suppressed upregulation of genes related to proteolysis and cellular senescence in muscle. We conclude that PMAT accumulation accelerates age- and obesity-induced muscle atrophy by increasing proteolysis and cellular senescence in muscle.
Topics: Adipose Tissue; Aging; Animals; Cellular Senescence; Disease Models, Animal; Forkhead Box Protein O1; Humans; Mice; Mice, Obese; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Obesity; Quality of Life; SKP Cullin F-Box Protein Ligases; Sarcopenia; Tripartite Motif Proteins; Ubiquitin-Protein Ligases
PubMed: 31442231
DOI: 10.1371/journal.pone.0221366 -
Scientific Reports Aug 2022Cortical atrophy is measured clinically according to established visual rating scales based on magnetic resonance imaging (MRI). Although brain MRI is the primary...
Cortical atrophy is measured clinically according to established visual rating scales based on magnetic resonance imaging (MRI). Although brain MRI is the primary imaging marker for neurodegeneration, computed tomography (CT) is also widely used for the early detection and diagnosis of dementia. However, they are seldom investigated. Therefore, we developed a machine learning algorithm for the automatic estimation of cortical atrophy on brain CT. Brain CT images (259 Alzheimer's dementia and 55 cognitively normal subjects) were visually rated by three neurologists and used for training. We constructed an algorithm by combining the convolutional neural network and regularized logistic regression (RLR). Model performance was then compared with that of neurologists, and feature importance was measured. RLR provided fast and reliable automatic estimations of frontal atrophy (75.2% accuracy, 93.6% sensitivity, 67.2% specificity, and 0.87 area under the curve [AUC]), posterior atrophy (79.6% accuracy, 87.2% sensitivity, 75.9% specificity, and 0.88 AUC), right medial temporal atrophy (81.2% accuracy, 84.7% sensitivity, 79.6% specificity, and 0.88 AUC), and left medial temporal atrophy (77.7% accuracy, 91.1% sensitivity, 72.3% specificity, and 0.90 AUC). We concluded that RLR-based automatic estimation of brain CT provided a comprehensive rating of atrophy that can potentially support physicians in real clinical settings.
Topics: Alzheimer Disease; Atrophy; Brain; Humans; Machine Learning; Magnetic Resonance Imaging; Neuroimaging; Tomography, X-Ray Computed
PubMed: 36042322
DOI: 10.1038/s41598-022-18696-6 -
The Journal of Physiology Feb 2023Most cells in the body are mononuclear whereas skeletal muscle fibres are uniquely multinuclear. The nuclei of muscle fibres (myonuclei) are usually situated... (Review)
Review
Most cells in the body are mononuclear whereas skeletal muscle fibres are uniquely multinuclear. The nuclei of muscle fibres (myonuclei) are usually situated peripherally which complicates the equitable distribution of gene products. Myonuclear abundance can also change under conditions such as hypertrophy and atrophy. Specialised zones in muscle fibres have different functions and thus distinct synthetic demands from myonuclei. The complex structure and regulatory requirements of multinuclear muscle cells understandably led to the hypothesis that myonuclei govern defined 'domains' to maintain homeostasis and facilitate adaptation. The purpose of this review is to provide historical context for the myonuclear domain and evaluate its veracity with respect to mRNA and protein distribution resulting from myonuclear transcription. We synthesise insights from past and current in vitro and in vivo genetically modified models for studying the myonuclear domain under dynamic conditions. We also cover the most contemporary knowledge on mRNA and protein transport in muscle cells. Insights from emerging technologies such as single myonuclear RNA-sequencing further inform our discussion of the myonuclear domain. We broadly conclude: (1) the myonuclear domain can be flexible during muscle fibre growth and atrophy, (2) the mechanisms and role of myonuclear loss and motility deserve further consideration, (3) mRNA in muscle is actively transported via microtubules and locally restricted, but proteins may travel far from a myonucleus of origin and (4) myonuclear transcriptional specialisation extends beyond the classic neuromuscular and myotendinous populations. A deeper understanding of the myonuclear domain in muscle may promote effective therapies for ageing and disease.
Topics: Adult; Humans; Muscle, Skeletal; Muscle Fibers, Skeletal; Cell Nucleus; RNA, Messenger; Atrophy
PubMed: 36629254
DOI: 10.1113/JP283658 -
Nature Materials Feb 2023While mechanical stimulation is known to regulate a wide range of biological processes at the cellular and tissue levels, its medical use for tissue regeneration and...
While mechanical stimulation is known to regulate a wide range of biological processes at the cellular and tissue levels, its medical use for tissue regeneration and rehabilitation has been limited by the availability of suitable devices. Here we present a mechanically active gel-elastomer-nitinol tissue adhesive (MAGENTA) that generates and delivers muscle-contraction-mimicking stimulation to a target tissue with programmed strength and frequency. MAGENTA consists of a shape memory alloy spring that enables actuation up to 40% strain, and an adhesive that efficiently transmits the actuation to the underlying tissue. MAGENTA activates mechanosensing pathways involving yes-associated protein and myocardin-related transcription factor A, and increases the rate of muscle protein synthesis. Disuse muscles treated with MAGENTA exhibit greater size and weight, and generate higher forces compared to untreated muscles, demonstrating the prevention of atrophy. MAGENTA thus has promising applications in the treatment of muscle atrophy and regenerative medicine.
Topics: Humans; Muscle, Skeletal; Tissue Adhesives; Rosaniline Dyes; Muscular Atrophy; Muscle Contraction
PubMed: 36357687
DOI: 10.1038/s41563-022-01396-x -
Multiple Sclerosis and Related Disorders Nov 2023Cognitive reserve (CR) describes an individual's ability to adapt cognitive processes in response to brain atrophy, and has been reported to explain some of the... (Review)
Review
BACKGROUND
Cognitive reserve (CR) describes an individual's ability to adapt cognitive processes in response to brain atrophy, and has been reported to explain some of the discrepancy between brain atrophy and cognitive functioning outcomes in multiple sclerosis (MS). CR in MS is typically investigated by assessing an individual's pre- and/or post-diagnosis enrichment, which includes premorbid intellectual abilities, educational level, occupational attainment, and engagement in cognitively enriching leisure activities. Common MS symptoms (e.g., physical disability, fatigue, depression, anxiety) may impact an individual's ability to engage in various CR-enhancing activities post-diagnosis. It is unknown to what extent these MS symptoms have been taken into account in MS research on CR. As such, we identified whether studies assessed CR using measures of premorbid or continuous (including post-diagnosis) enrichment. For studies investigating continuous enrichment, we identified whether studies accounted for MS-impact, which MS symptoms were accounted for, and how, and whether studies acknowledged MS symptoms as potential CR-confounds.
METHODS
Three electronic databases (PsycINFO, PubMed, Scopus) were searched. Eligible studies investigated CR proxies (e.g., estimated premorbid intellectual abilities, vocabulary knowledge, educational level, occupational attainment, cognitively enriching leisure activities, or a combination thereof) in relation to cognitive, brain atrophy or connectivity, or daily functioning outcomes in adult participants with MS. We extracted data on methods and measures used, including any MS symptoms taken into account. Objectives were addressed using frequency analyses and narrative synthesis.
RESULTS
115 studies were included in this review. 47.8% of all studies investigated continuous enrichment. Approximately half of the studies investigating continuous enrichment accounted for potential MS-impact in their analyses, with only 31.0% clearly identifying that they treated MS symptoms as potential confounds for CR-enhancement. A narrative synthesis of studies which investigated CR with and without controlling statistically for MS-impact indicated that accounting for MS symptoms may impact findings concerning the protective nature of CR.
CONCLUSION
Fewer than half of the studies investigating CR proxies in MS involved continuous enrichment. Just over half of these studies accounted for potential MS-impact in their analyses. To achieve a more complete and accurate understanding of CR in MS, future research should investigate both pre-MS and continuous enrichment. In doing so, MS symptoms and their potential impact should be considered. Establishing greater consistency and rigour across CR research in MS will be crucial to produce an evidence base for the development of interventions aimed at improving quality of care and life for pwMS.
Topics: Adult; Humans; Multiple Sclerosis; Cognitive Reserve; Brain; Depression; Anxiety; Atrophy; Fatigue
PubMed: 37806233
DOI: 10.1016/j.msard.2023.105017 -
European Journal of Neurology Jan 2022Globular glial tauopathies (GGTs) have heterogeneous presentations; little evidence regarding typical clinical and magnetic resonance imaging (MRI) presentations are...
BACKGROUND AND PURPOSE
Globular glial tauopathies (GGTs) have heterogeneous presentations; little evidence regarding typical clinical and magnetic resonance imaging (MRI) presentations are available.
METHODS
We retrospectively assessed MRIs from three postmortem-confirmed GGT cases, in two patients with atypical progressive aphasia and one with corticobasal syndrome.
RESULTS
We suggest that four principal concomitant MRI findings characterize GGT type I: a sagittal callosal hyperintense band, marked focal callosal atrophy suggesting white matter degeneration originating in cortical areas responsible for symptoms (anterior atrophy in predominantly language manifestations and posterior atrophy in predominantly apraxia), periventricular white matter lesions, and mild-to-moderate brain stem atrophy.
CONCLUSIONS
We observed four concomitant MRI abnormalities in patients with atypical dementia, parkinsonism, and late incomplete supranuclear gaze palsy. Two patients had atypical progressive aphasia and one had corticobasal syndrome.
Topics: Atrophy; Corpus Callosum; Humans; Neuroimaging; Retrospective Studies; Tauopathies
PubMed: 34469612
DOI: 10.1111/ene.15090 -
Brain : a Journal of Neurology May 2022Genetic therapy has changed the prognosis of hereditary proximal spinal muscular atrophy, although treatment efficacy has been variable. There is a clear need for deeper...
Genetic therapy has changed the prognosis of hereditary proximal spinal muscular atrophy, although treatment efficacy has been variable. There is a clear need for deeper understanding of underlying causes of muscle weakness and exercise intolerance in patients with this disease to further optimize treatment strategies. Animal models suggest that in addition to motor neuron and associated musculature degeneration, intrinsic abnormalities of muscle itself including mitochondrial dysfunction contribute to the disease aetiology. To test this hypothesis in patients, we conducted the first in vivo clinical investigation of muscle bioenergetics. We recruited 15 patients and 15 healthy age and gender-matched control subjects in this cross-sectional clinico-radiological study. MRI and 31P magnetic resonance spectroscopy, the modality of choice to interrogate muscle energetics and phenotypic fibre-type makeup, was performed of the proximal arm musculature in combination with fatiguing arm-cycling exercise and blood lactate testing. We derived bioenergetic parameter estimates including: blood lactate, intramuscular pH and inorganic phosphate accumulation during exercise, and muscle dynamic recovery constants. A linear correlation was used to test for associations between muscle morphological and bioenergetic parameters and clinico-functional measures of muscle weakness. MRI showed significant atrophy of triceps but not biceps muscles in patients. Maximal voluntary contraction force normalized to muscle cross-sectional area for both arm muscles was 1.4-fold lower in patients than in controls, indicating altered intrinsic muscle properties other than atrophy contributed to muscle weakness in this cohort. In vivo31P magnetic resonance spectroscopy identified white-to-red remodelling of residual proximal arm musculature in patients on the basis of altered intramuscular inorganic phosphate accumulation during arm-cycling in red versus white and intermediate myofibres. Blood lactate rise during arm-cycling was blunted in patients and correlated with muscle weakness and phenotypic muscle makeup. Post-exercise metabolic recovery was slower in residual intramuscular white myofibres in patients demonstrating mitochondrial ATP synthetic dysfunction in this particular fibre type. This study provides the first in vivo evidence in patients that degeneration of motor neurons and associated musculature causing atrophy and muscle weakness in 5q spinal muscular atrophy type 3 and 4 is aggravated by disproportionate depletion of myofibres that contract fastest and strongest. Our finding of decreased mitochondrial ATP synthetic function selectively in residual white myofibres provides both a possible clue to understanding the apparent vulnerability of this particular fibre type in 5q spinal muscular atrophy types 3 and 4 as well as a new biomarker and target for therapy.
Topics: Adenosine Triphosphate; Atrophy; Humans; Lactates; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mitochondria; Muscle Weakness; Muscle, Skeletal; Muscular Atrophy; Muscular Atrophy, Spinal; Phosphates
PubMed: 34788410
DOI: 10.1093/brain/awab411 -
Anesthesiology Sep 2019Muscle atrophy is common in the critically ill, and diaphragm atrophy occurs during mechanical ventilation. It is not known whether wasting of diaphragm and nondiaphragm... (Observational Study)
Observational Study
WHAT WE ALREADY KNOW ABOUT THIS TOPIC
Muscle atrophy is common in the critically ill, and diaphragm atrophy occurs during mechanical ventilation. It is not known whether wasting of diaphragm and nondiaphragm muscle is related.
WHAT THIS ARTICLE TELLS US THAT IS NEW
Ultrasound was used for serial assessment of diaphragm and pectoral muscle in 97 critically ill patients. Diaphragm and pectoral atrophy occurred in 48% and 29%, respectively, and was associated with septic shock (diaphragm) and steroid use (pectoral); atrophy of the two muscle types appears unrelated.
BACKGROUND
Muscle atrophy occurs early during critical illnesses. Although diffuse, this atrophy may specifically affect the diaphragm under artificial inactivity accompanying invasive mechanical ventilation. The primary objective of this study was to highlight diaphragm atrophy during the first 5 days of critical illness. Monitoring of pectoral thickness (a nonpostural muscle with mainly phasic function) served as a control.
METHODS
Diaphragm and pectoral thicknesses were measured by ultrasound within the first 24 h of admission in 97 critically ill patients, including 62 on mechanical ventilation. Thirty-five patients were reexamined at day 5.
RESULTS
Baseline median (interquartile) values of diaphragm and pectoral thicknesses at day 1 were 2.4 (2.0, 2.9) and 5.9 (4.7, 7.2) mm, respectively (n = 97). Higher values of diaphragm thickness at baseline were positively associated with male sex, chronic obstructive pulmonary disease, and diabetes. Diaphragm and pectoral atrophies (defined as a decrease of 10% or more between day 1 and day 5) were detected in 48% (17 of 35) and 29% (10 of 34) respectively, and were uncorrelated with each other. Diaphragm atrophy was significantly more frequent in patients with septic shock and in those with mechanical ventilation, as compared with their respective counterparts (71% [10 of 14] vs. 33% [7 of 21], P = 0.027 and 71% [17 of 28] vs. 0% [0 of 7], P = 0.004, respectively), whereas pectoral atrophy was more common in patients treated with steroids as compared with their counterparts (58% [7 of 12] vs. 14% [3 of 22], P = 0.006). A statistically significant association between diaphragm atrophy and outcome was not found. Pectoral atrophy seemed associated with less successful weaning from mechanical ventilation at day 14 (12% [1 of 8] vs. 58% [11 of 19], P = 0.043).
CONCLUSIONS
Ultrasound enables identification of specific early diaphragm atrophy that affects the majority of mechanically ventilated patients and septic shock patients. Diaphragm atrophy and pectoral muscle atrophy seem to be two unrelated processes.
Topics: Aged; Critical Illness; Diaphragm; Female; Humans; Male; Middle Aged; Muscular Atrophy; Pectoralis Muscles; Prospective Studies; Respiration, Artificial; Ultrasonography
PubMed: 31094757
DOI: 10.1097/ALN.0000000000002737 -
Scientific Reports Mar 2021The mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of... (Observational Study)
Observational Study
The mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of this study was to assess neurodevelopmental outcome in 10-year-old children with HIE with and without therapeutic hypothermia. Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at school-age. Ten-year-old children with HIE were included, who were treated with therapeutic hypothermia (n = 22) or would have qualified but were born before this became standard of care (n = 28). Children completed a neuropsychological and motor assessment and MRI. Mammillary bodies were scored as normal or atrophic at 10 years. Brain volumes were segmented on childhood MRI and DTI scans were analysed using tract-based spatial statistics. Children with HIE suffered from neurocognitive and memory problems at school-age, irrespective of hypothermia. Hippocampal volumes and MB atrophy were associated with total and performance IQ, processing speed and episodic memory in both groups. Normal MB and larger hippocampi were positively associated with global fractional anisotropy. In conclusion, injury to the MB and hippocampi was associated with neurocognition and memory at school-age in HIE and might be an early biomarker for neurocognitive and memory problems.
Topics: Anisotropy; Atrophy; Child; Diffusion Tensor Imaging; Female; Hippocampus; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Male; Mammillary Bodies; Memory; Netherlands; Neuropsychological Tests; Psychomotor Performance; Retrospective Studies; Schools; Students; White Matter
PubMed: 33658541
DOI: 10.1038/s41598-021-83982-8 -
European Radiology Dec 2021
Topics: Humans; Atrophy; Temporal Lobe
PubMed: 34599666
DOI: 10.1007/s00330-021-08340-8