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American Journal of Physiology.... Jul 2022Skeletal muscle is an integral tissue system that plays a crucial role in the physical function of all vertebrates and is a key target for maintaining or improving... (Review)
Review
Skeletal muscle is an integral tissue system that plays a crucial role in the physical function of all vertebrates and is a key target for maintaining or improving health and performance across the lifespan. Based largely on cellular and animal models, there is some evidence that various forms of heat stress with or without resistance exercise may enhance skeletal muscle growth or reduce its loss. It is not clear whether these stimuli are similarly effective in humans or meaningful compared with exercise alone across various heating methodologies. Furthermore, the magnitude by which heat stress may influence whole body thermoregulatory responses and the connection to skeletal muscle adaptation remains ambiguous. Finally, the underlying mechanisms, which may include interaction between relevant heat shock proteins and intracellular hypertrophy and atrophy related factors, remain unclear. In this narrative review, we examine the relevant literature regarding heat stress alone or in combination with resistance exercise emphasizing skeletal muscle hypertrophy and atrophy across cellular and animal models, as well as human investigations. In addition, we present working mechanistic theories for heat shock protein-mediated signaling effects regarding hypertrophy and atrophy-related signaling processes. Importantly, continued research is necessary to determine the practical effects and mechanisms of heat stress with and without resistance exercise on skeletal muscle function via growth and maintenance.
Topics: Animals; Atrophy; Exercise; Heat-Shock Proteins; Heat-Shock Response; Hypertrophy; Muscle, Skeletal; Muscular Atrophy
PubMed: 35536704
DOI: 10.1152/ajpregu.00048.2022 -
Journal of Cellular and Molecular... Sep 2022Homeostasis in skeletal muscle is sustained by the balance of functional and physical interactions between muscle and myofibre microenvironment. Various factors, such as... (Review)
Review
Homeostasis in skeletal muscle is sustained by the balance of functional and physical interactions between muscle and myofibre microenvironment. Various factors, such as ageing, disuse and denervation, tip the balance and induce skeletal muscle atrophy. Skeletal muscle atrophy, which involves complex physiological and biochemical changes, is accompanied by adverse outcomes and even increased mortality. Multiple studies have investigated the role of neutrophils in atrophied skeletal muscles; however, neutrophil intrusion in muscle is still a polemical knot. As technical obstacles have been overcome, people have gradually discovered new functions of neutrophils. The classical view of neutrophils is no longer applicable to their biological characteristics. To date, no clear association between the hidden injurious effect of neutrophil intrusion and muscle atrophy has been convincingly proven. Throughout this review, we have discussed the neutrophil activities that mediate muscle atrophy for distinct disease occurrences. Hopefully, this review will help both clinicians and researchers of skeletal muscle atrophy with relevant targets to further explore efficient medical interventions and treatments.
Topics: Aging; Humans; Muscle, Skeletal; Muscular Atrophy; Neutrophils
PubMed: 35899367
DOI: 10.1111/jcmm.17495 -
Pain Medicine (Malden, Mass.) Dec 2023Chronic low back pain (CLBP) is multifactorial in nature, with recent research highlighting the role of multifidus dysfunction in a subset of nonspecific CLBP. This... (Review)
Review
OBJECTIVE
Chronic low back pain (CLBP) is multifactorial in nature, with recent research highlighting the role of multifidus dysfunction in a subset of nonspecific CLBP. This review aimed to provide a foundational reference that elucidates the pathophysiological cascade of multifidus dysfunction, how it contrasts with other CLBP etiologies and the role of restorative neurostimulation.
METHODS
A scoping review of the literature.
RESULTS
In total, 194 articles were included, and findings were presented to highlight emerging principles related to multifidus dysfunction and restorative neurostimulation. Multifidus dysfunction is diagnosed by a history of mechanical, axial, nociceptive CLBP and exam demonstrating functional lumbar instability, which differs from other structural etiologies. Diagnostic images may be used to grade multifidus atrophy and assess other structural pathologies. While various treatments exist for CLBP, restorative neurostimulation distinguishes itself from traditional neurostimulation in a way that treats a different etiology, targets a different anatomical site, and has a distinctive mechanism of action.
CONCLUSIONS
Multifidus dysfunction has been proposed to result from loss of neuromuscular control, which may manifest clinically as muscle inhibition resulting in altered movement patterns. Over time, this cycle may result in potential atrophy, degeneration and CLBP. Restorative neurostimulation, a novel implantable neurostimulator system, stimulates the efferent lumbar medial branch nerve to elicit repetitive multifidus contractions. This intervention aims to interrupt the cycle of dysfunction and normalize multifidus activity incrementally, potentially restoring neuromuscular control. Restorative neurostimulation has been shown to reduce pain and disability in CLBP, improve quality of life and reduce health care expenditures.
Topics: Humans; Paraspinal Muscles; Quality of Life; Low Back Pain; Lumbosacral Region; Atrophy
PubMed: 37439698
DOI: 10.1093/pm/pnad098 -
Stem Cell Research & Therapy Jun 2022Skeletal muscle mass and function losses in aging individuals are associated with quality of life deterioration and disability. Mesenchymal stromal cells exert...
Human umbilical cord-derived mesenchymal stromal cells ameliorate aging-associated skeletal muscle atrophy and dysfunction by modulating apoptosis and mitochondrial damage in SAMP10 mice.
BACKGROUND
Skeletal muscle mass and function losses in aging individuals are associated with quality of life deterioration and disability. Mesenchymal stromal cells exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in aging-related degenerative disease.
METHODS AND RESULTS
We investigated the efficacy of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) on sarcopenia-related skeletal muscle atrophy and dysfunction in senescence-accelerated mouse prone 10 (SAMP10) mice. We randomly assigned 24-week-old male SAMP10 mice to a UC-MSC treatment group and control group. At 12 weeks post-injection, the UC-MSC treatment had ameliorated sarcopenia-related muscle changes in performance, morphological structures, and mitochondria biogenesis, and it enhanced the amounts of proteins or mRNAs for myosin heavy chain, phospho-AMP-activated protein kinase, phospho-mammalian target of rapamycin, phospho-extracellular signal-regulated kinase1/2, peroxisome proliferator-activated receptor-γ coactivator, GLUT-4, COX-IV, and hepatocyte growth factor in both gastrocnemius and soleus muscles, and it reduced the levels of proteins or mRNAs for cathepsin K, cleaved caspase-3/-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and gp91 mRNAs. The UC-MSC treatment retarded mitochondria damage, cell apoptosis, and macrophage infiltrations, and it enhanced desmin/laminin expression and proliferating and CD34/Integrin α cells in both types of skeletal muscle of the SAMP10 mice. In vitro, we observed increased levels of HGF, PAX-7, and MoyD mRNAs at the 4th passage of UC-MSCs.
CONCLUSIONS
Our results suggest that UC-MSCs can improve sarcopenia-related skeletal muscle atrophy and dysfunction via anti-apoptosis, anti-inflammatory, and mitochondrial biogenesis mechanisms that might be mediated by an AMPK-PGC1-α axis, indicating that UC-MSCs may provide a promising treatment for sarcopenia/muscle diseases.
Topics: Aging; Animals; Apoptosis; Humans; Male; Mammals; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Muscle, Skeletal; Muscular Atrophy; Quality of Life; Sarcopenia; Umbilical Cord
PubMed: 35659361
DOI: 10.1186/s13287-022-02895-z -
Human Brain Mapping May 2023Visual impairment and retinal neurodegeneration are intrinsically connected and both have been associated with cognitive impairment and brain atrophy, but the underlying...
Visual impairment and retinal neurodegeneration are intrinsically connected and both have been associated with cognitive impairment and brain atrophy, but the underlying mechanisms remain unclear. To investigate whether transneuronal degeneration is implicated, we systematically assessed the relation between visual function and retinal, visual pathway, hippocampal and brain degeneration. We analyzed baseline data from 3316 eligible Rhineland Study participants with visual acuity (VA), optical coherence tomography (OCT), and magnetic resonance imaging (MRI) data available. Regional volumes, cortical volume, and fractional anisotropy (FA) were derived from T1-weighted and diffusion-weighted 3 T MRI scans. Statistical analyses were performed using multivariable linear regression and structural equation modeling. VA and ganglion cell layer (GCL) thinning were both associated with global brain atrophy (SD effect size [95% CI] -0.090 [-0.118 to -0.062] and 0.066 [0.053-0.080], respectively), and hippocampal atrophy (-0.029 [-0.055 to -0.003] and 0.114 [0.087-0.141], respectively). The effect of VA on whole brain and hippocampal volume was partly mediated by retinal neurodegeneration. Similarly, the effect of retinal neurodegeneration on brain and hippocampal atrophy was mediated through intermediate visual tracts, accounting for 5.2%-23.9% of the effect. Visual impairment and retinal neurodegeneration were robustly associated with worse brain atrophy, FA, and hippocampal atrophy, partly mediated through disintegration of intermediate visual tracts. Our findings support the use of OCT-derived retinal measures as markers of neurodegeneration, and indicate that both general and transneuronal neurodegeneration along the visual pathway, partly reflecting visual impairment, account for the association between retinal neurodegeneration and brain atrophy.
Topics: Humans; Retina; Brain; Magnetic Resonance Imaging; Vision Disorders; Atrophy
PubMed: 36852616
DOI: 10.1002/hbm.26237 -
Acta Neuropathologica Nov 2019Alzheimer's disease (AD) differentially and specifically affects brain regions and neuronal cell types in a predictable pattern. Damage to the brain appears to spread... (Review)
Review
Alzheimer's disease (AD) differentially and specifically affects brain regions and neuronal cell types in a predictable pattern. Damage to the brain appears to spread and worsens with time, taking over more regions and activating multiple stressors that can converge to promote vulnerability of certain cell types. At the same time, other cell types and brain regions remain intact in the face of this onslaught of neuropathology. Although neuropathologic descriptions of AD have been extensively expanded and mapped over the last several decades, our understanding of the mechanisms underlying how certain regions and cell populations are specifically vulnerable or resistant has lagged behind. In this review, we detail what is known about the selectivity of local initiation of AD pathology in the hippocampus, its proposed spread via synaptic connections, and the diversity of clinical phenotypes and brain atrophy patterns that may arise from different fibrillar strains of pathologic proteins or genetic predispositions. We summarize accumulated and emerging knowledge of the cellular and molecular basis for neuroanatomic selectivity, consider potential disease-relevant differences between vulnerable and resistant neuronal cell types and isolate molecular markers to identify them.
Topics: Alzheimer Disease; Atrophy; Brain; Genetic Predisposition to Disease; Humans; Neurons; Neuropathology
PubMed: 31392412
DOI: 10.1007/s00401-019-02054-4 -
Journal of Neuroimaging : Official... Nov 2022Subtle cognitive decline represents a stage of cognitive deterioration in which pathological biomarkers may be present, including early cortical atrophy and amyloid...
BACKGROUND AND PURPOSE
Subtle cognitive decline represents a stage of cognitive deterioration in which pathological biomarkers may be present, including early cortical atrophy and amyloid deposition. Using individual items from the Montreal Cognitive Assessment and k-modes cluster analysis, we previously identified three clusters of individuals without overt cognitive impairment: (1) High Performing (no deficits in performance), (2) Memory Deficits (lower memory performance), and (3) Compound Deficits (lower memory and executive function performance). In this study, we sought to understand the relationships found in our clusters between cortical atrophy on MR and amyloid burden on PET.
METHODS
Data were derived from the Alzheimer's Disease Neuroimaging Initiative and comprised individuals from our previous analyses with available MR and amyloid PET scans (n = 272). Using multiple-group structural equation modeling, we regressed amyloid standardized uptake value ratio on volumetric regions to simultaneously evaluate unique associations within each cluster.
RESULTS
In our Compound Deficits cluster, greater whole cerebral amyloid burden was significantly related to right entorhinal cortical and left hippocampal atrophy, r = -.412 (p = .005) and -.304 (p = .049), respectively. Within this cluster, right entorhinal cortical atrophy was significantly related to greater amyloid burden within multiple frontal regions.
CONCLUSIONS
The Compound Deficits cluster, which represents a group potentially at higher risk for decline, was observed to have significantly more cortical atrophy, particularly within the entorhinal cortex and hippocampus, associated with whole brain and frontal lobe amyloid burden. These findings point to a pattern of early pathological deterioration that may place these individuals at risk for future decline.
Topics: Humans; Amyloid beta-Peptides; Magnetic Resonance Imaging; Cognitive Dysfunction; Atrophy; Amyloid; Alzheimer Disease; Positron-Emission Tomography; Brain; Amyloidosis; Amyloidogenic Proteins
PubMed: 36151065
DOI: 10.1111/jon.13055 -
European Journal of Neurology Nov 2022Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and fluoro-deoxy-glucose positron emission tomography (FDG-PET)...
BACKGROUND AND PURPOSE
Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and fluoro-deoxy-glucose positron emission tomography (FDG-PET) features of LO and EO posterior cortical atrophy (LO_PCA, EO_PCA), the visual variant of Alzheimer's disease (AD), were compared. LO_PCA patients were also compared with a group of patients with LO typical AD (tAD).
METHODS
Thirty-seven LO_PCA patients (onset age ≥ 65 years), 29 EO_PCA patients and 40 tAD patients who all underwent a standard neuropsychological battery were recruited; PCA patients were also assessed for the presence of posterior signs and symptoms. Brain FDG-PET was available in 32 LO_PCA cases, 23 EO_PCA cases and all tAD cases, and their scans were compared with scans from 30 healthy elderly controls. Within the entire PCA sample FDG uptake was also correlated with age at onset as a continuous variable.
RESULTS
The main difference between the two PCA groups was a higher prevalence of Bálint-Holmes symptoms in EO cases, which was associated with the presence of severe bilateral occipito-temporo-parietal hypometabolism, whilst LO_PCA patients showed reduction of FDG uptake mainly in the right posterior regions. The latter group also showed mesial temporal hypometabolism, similarly to the tAD group, although with a right rather than left lateralization. Correlation analysis confirmed the association between older age and decreased limbic metabolism and between younger age and decreased left parietal metabolism.
CONCLUSIONS
The major involvement of the temporal cortex in LO cases and of the parietal cortex in EO cases reported previously within the AD spectrum holds true also for the visual variant of AD.
Topics: Aged; Alzheimer Disease; Atrophy; Fluorodeoxyglucose F18; Glucose; Humans; Positron-Emission Tomography
PubMed: 35950612
DOI: 10.1111/ene.15520 -
Translational Research : the Journal of... Jul 2020The age-associated decline in muscle mass has become synonymous with physical frailty among the elderly due to its major contribution in reduced muscle function.... (Review)
Review
The age-associated decline in muscle mass has become synonymous with physical frailty among the elderly due to its major contribution in reduced muscle function. Alterations in protein and redox homeostasis along with chronic inflammation, denervation, and hormonal dysregulation are all hallmarks of muscle wasting and lead to clinical sarcopenia in older adults. Reduction in skeletal muscle mass has been observed and reported in the scientific literature for nearly 2 centuries; however, identification and careful examination of molecular mediators of age-related muscle atrophy have only been possible for roughly 3 decades. Here we review molecular targets of recent interest in age-related muscle atrophy and briefly discuss emerging small molecule therapeutic treatments for muscle wasting in sarcopenic susceptible populations.
Topics: Aging; Humans; Muscle, Skeletal; Muscular Atrophy
PubMed: 32243876
DOI: 10.1016/j.trsl.2020.03.001 -
Anatomical Record (Hoboken, N.J. : 2007) Jul 2021Thirty million people are infected with human immunodeficiency virus (HIV) worldwide, and HIV-associated neurocognitive disorder (HAND) is one of the most common... (Review)
Review
Thirty million people are infected with human immunodeficiency virus (HIV) worldwide, and HIV-associated neurocognitive disorder (HAND) is one of the most common comorbidities of HIV. However, the effect of HIV on the brain has not been fully investigated. This article aimed to review the changes to the brain due to HIV in terms of atrophy, diffusion changes, and hyperintensities. Studies have observed significant atrophy in subcortical gray matter, as well as in cortical white and gray matter. Moreover, the ventricles enlarge, and the sulci widen. Although HIV causes changes to the white and gray matter of the brain, few diffusion tensor imaging studies have investigated the changes to gray matter integrity. White and gray matter hyperintensities have frequently been observed in HIV-positive individuals, with the subcortical gray matter (caudate nucleus and putamen) and periventricular white matter frequently affected. In conclusion, subcortical gray matter is the first brain region to be affected and is affected most severely. Additionally, this review highlights the gaps in the literature, since the effect of HIV on the brain is not fully known. Future studies should continue to investigate the effect of HIV on the brain in different stages of the disease, and alternate therapies should be developed since highly active antiretroviral therapy is currently ineffective at treating HAND.
Topics: Atrophy; Brain; Diffusion Tensor Imaging; HIV; HIV Infections; Humans
PubMed: 33231355
DOI: 10.1002/ar.24573