Neuromuscular Processes Research Articles

Lights, Chemicals, Action: Studying Red Worms' Responses to Environmental Contaminants.

We have developed an experimental module that introduces high school students to guided scientific inquiry. It is designed to incorporate environmental health and ecological concepts into the basic biology or environmental-science content of the high school curriculum. Using the red worm, a familiar live species that is amenable to classroom experimentation, students learn how environmental agents affect the animal's locomotion by altering sensory neuron-muscle interactions and, as a result, influence its distribution in nature. In turn, the results of these experiments have direct application to human-caused environmental disruptions that cause changes in species distribution and indirectly increase the recognition that environmental chemicals affect human health. Students undertake a series of explorations to identify how red worms sense their environment and then apply that knowledge to understand the effects of chemical exposure on locomotor behavior. The activities are designed to generate critical thinking about neuromuscular processes and environmental pollutants that affect them.

Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury.

Traumatic brain injury (TBI) contributes to the increased rates of suicide and post-traumatic stress disorder in military personnel and veterans, and it is also associated with the risk for neurodegenerative and psychiatric disorders. A cross-phenotype high-resolution polygenic risk score (PRS) analysis of persistent post-concussive symptoms (PCS) was conducted in 845 U.S. Army soldiers who sustained TBI during their deployment. We used a prospective longitudinal survey of three brigade combat teams to assess deployment-acquired TBI and persistent physical, cognitive, and emotional PCS. PRS was derived from summary statistics of large genome-wide association studies of Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, and major depressive disorder (MDD); and for years of schooling, college completion, childhood intelligence, infant head circumference (IHC), and adult intracranial volume. Although our study had more than 95% of statistical power to detect moderate-to-large effect sizes, no association was observed with neurodegenerative and psychiatric disorders, suggesting that persistent PCS does not share genetic components with these traits to a moderate-to-large degree. We observed a significant finding: subjects with high IHC PRS recovered better from cognitive/emotional persistent PCS than the other individuals (R2 = 1.11%; p = 3.37 × 10-3). Enrichment analysis identified two significant Gene Ontology (GO) terms related to this result: GO:0050839∼Cell adhesion molecule binding (p = 8.9 × 10-6) and GO:0050905∼Neuromuscular process (p = 9.8 × 10-5). In summary, our study indicated that the genetic predisposition to persistent PCS after TBI does not have substantial overlap with neurodegenerative and psychiatric diseases, but mechanisms related to early brain growth may be involved.

Kinematic and Spatio-Temporal Characteristics of Gait in Blind Individuals

Introduction: Visual inputs in the neuromuscular response process of the central nerve system have an important role in various motor tasks. The identification of the influence of lack of visual input on gait in blind people may be useful in rehabilitation planning and correction of gait pattern. The aims of this study were to compare spatio-temporal variables and the symmetry index of gait among blind and healthy individuals, and investigate the effects of closing the eyes on kinematics of gait in healthy subjects. Materials and Methods: In the present study, 10 blind and 10 healthy subjects with similar age, height, and mass participated. Spatio-temporal variables of gait were measured in blind subjects without a cane and in normal subjects with and without vision. The differences between the two groups and the two walking conditions were determined through repeated measure and significance level of P < 0.05. Results: Stride length, step length, and gait velocity were lower in blind individuals than healthy individuals with vision (P < 0.05). Stride length, step length, and stride time in healthy individuals without vision were greater than in blind individuals. In healthy individuals without vision, stride and step time, fluctuation time, and single support time were increased while cadence was decreased. Moreover, the asymmetry index in the healthy group without vision in terms of variables of single support time, fluctuation time, and toe raised off the ground time had greater symmetry than the blind subjects. Conclusion: Blindness is accompanied with reduced walking speed and step and stride length. Lack of vision in healthy subjects, caused increased stride time, single support time, and fluctuation time and decreased cadence. Stride length, step length, and stride time in healthy subjects without vision were greater than in blind individuals. It seems that the role of proprioceptive receptors is more pronounced in blind individuals than normal individuals.

Control of lung ventilation following overwintering conditions in bullfrogs, Lithobates catesbeianus.

Ranid frogs in northern latitudes survive winter at cold temperatures in aquatic habitats often completely covered by ice. Cold-submerged frogs survive aerobically for several months relying exclusively on cutaneous gas exchange while maintaining temperature-specific acid-base balance. Depending on the overwintering hibernaculum, frogs in northern latitudes could spend several months without access to air, the need to breathe or the chemosensory drive to use neuromuscular processes that regulate and enable pulmonary ventilation. Therefore, we performed experiments to determine whether aspects of the respiratory control system of bullfrogs, Lithobates catesbeianus, are maintained or suppressed following minimal use of air breathing in overwintering environments. Based on the necessity for control of lung ventilation in early spring, we hypothesized that critical components of the respiratory control system of bullfrogs would be functional following simulated overwintering. We found that bullfrogs recently removed from simulated overwintering environments exhibited similar resting ventilation when assessed at 24°C compared with warm-acclimated control bullfrogs. Additionally, ventilation met resting metabolic and, presumably, acid-base regulation requirements, indicating preservation of basal respiratory function despite prolonged disuse in the cold. Recently emerged bullfrogs underwent similar increases in ventilation during acute oxygen lack (aerial hypoxia) compared with warm-acclimated frogs; however, CO2-related hyperventilation was significantly blunted following overwintering. Overcoming challenges to gas exchange during overwintering have garnered attention in ectothermic vertebrates, but this study uncovers robust and labile aspects of the respiratory control system at a time point correlating with early spring following minimal to no use of lung breathing in cold-aquatic overwintering habitats.

Influence of musical groove on postural sway.

Timescales of postural fluctuation reflect underlying neuromuscular processes in balance control that are influenced by sensory information and the performance of concurrent cognitive and motor tasks. An open question is how postural fluctuations entrain to complex environmental rhythms, such as in music, which also vary on multiple timescales. Musical groove describes the property of music that encourages auditory-motor synchronization and is used to study voluntary motor entrainment to rhythmic sounds. The influence of groove on balance control mechanisms remains unexplored. We recorded fluctuations in center of pressure (CoP) of standing participants (N = 40) listening to low and high groove music and during quiet stance. We found an effect of musical groove on radial sway variability, with the least amount of variability in the high groove condition. In addition, we observed that groove influenced postural sway entrainment at various temporal scales. For example, with increasing levels of groove, we observed more entrainment to shorter, local timescale rhythmic musical occurrences. In contrast, we observed more entrainment to longer, global timescale features of the music, such as periodicity, with decreasing levels of groove. Finally, musical experience influenced the amount of postural variability and entrainment at local and global timescales. We conclude that groove in music and musical experience can influence the neural mechanisms that govern balance control, and discuss implications of our findings in terms of multiscale sensorimotor coupling. (PsycINFO Database Record

Influence of Exchanged Neuromuscular Regulation of M.Gastrocnemius on Leg Bloodflow Regulation During Static Voluntary Contraction of Knee Flexors

Abstract In literature from 1970th are described experimentaly proved concept of muscle local blood flow redistribution to capillaries feeding active muscle fibres, and loss of this synhrone blood flow redistribution with changes of recruited motor units, caused by mechanical, metabolic or neural regulatory disturbances. On the other hand, from theory of applied kinesiology (AK) it is known that different external or internal challenges coud exchenge neuromuscular regulation and muscle could become weak-testing or become hypertonic. The physiological background of these changes is not jet known. The aim of this study is to find out connections between muscle's neuromuscular regulation and its local blood flow regulation. We investigate blood flow regulation in the leg during static voluntary contraction with contraction force 5% of the knee flexor muscle maximal static voluntary contraction (MVC) in position with knee flexed till 60 deg. In this experiment participate 8 LASE students in age 22-24 with normotonic m. gastrocnemius and 8 LASE students in age 22-26 with weak-tested m. gastrocnemius. Muscle tests were performed according AK testing methode (Frost, 2002.). Leg blood flow was measured with a mercury-in-silastic strain-gauge plethismograph, using the venous-occlusion plethismography Hokanson AI6 (Hokanson, Sumner and Strandness, 1975). Cycle of leg blood flow measurement was 15 seconds repeated twice in every controled minute. Student paired t-test was used to evaluate diferences in the results of blood flow measurements from strong tested and weak tested leg muscles. We find statistically significant (P&gt;95) differences triceps surae during static contraction with contracting force of knee flexors 5% MVC. Volume blood flow in leg with exchanged neuromuscular regulation of knee flexors where statisticaly higher neither blood floww in leg with normal neuromuscuular regulation. These differences was observed all the time of the static contraction. Changes of neuromuscular regulation could cause muscles local blood flow regulatory disturbances. Character of muscle local blood flow could be a quantitatively measurable parameter which reflects changes of neuromuscular regulatory processes of studied muscle.

Paralyzed Diaphragm

Diaphragmatic dysfunction may be unilateral or bilateral, with symptoms ranging from dyspnea only on extreme exertion to ventilator dependence. The etiology, treatment, and prognosis are quite different in unilateral and bilateral paralysis. A paralyzed hemidiaphragm may occur in isolation or as part of a systemic disease, whereas bilateral diaphragmatic paralysis usually occurs as a result of a traumatic or neuromuscular degenerative process. This review covers clinical evaluation, investigative studies, and management of diaphragmatic dysfunction. Figures show diaphragmatic motion during respiration, a postoperative radiograph from a 55-year-old woman who underwent left upper lobectomy, a postoperative radiograph of a 70-year-old man who underwent left upper lobectomy for removal of a peripheral 3 cm lesion, three chest radiographs of a 25-year-old man with a residual anterior mediastinal mass after treatment for germ cell tumor, chest radiograph showing left diaphragmatic paralysis in a breast cancer patient with malignant adenopathy involving the left phrenic nerve near the left main pulmonary artery, several parallel rows of sutures placed in the muscular portion and central tendon of the diaphragm and tied with the aid of a knot pusher, a laparoscopic mapping probe held onto the left diaphragm with suction and which receives electrical stimuli from an external clinical station, an electrode implant device that houses the electrode in the needle and is placed into the diaphragm tangentially, and the diaphragm pacing system programmed for conditioning and attached via percutaneously placed diaphragm electrodes in a spinal cord-injured child for early conditioning and weaning from the ventilator. Tables list causes of isolated diaphragmatic paralysis, general causes of unilateral and bilateral diaphragmatic paralysis, and differential diagnosis of elevated hemidiaphragm on chest radiograph. A video shows current technique of laparoscopic diaphragm pacemaker insertion. This review contains 9 highly rendered figures, 3 tables, 1 video, and 22 references

CLINICAL CASE OF LAMBERT EATON MYASTHENIC SYNDROME ON THE BACKGROUND OF ASYMPTOMATIC SMALL CELL LUNG CARCINOMA

This paper presents a case of Lambert-Eaton myasthenic syndrome (LEMS) of a man 54 years old. Manifestation of LEMS at 8 months ahead of identifying asymptomatic developing central lung cancer. Combined influence on the neuromuscular autoimmune and neoplastic processes led to complete remission of the LEMS and the absence progression of cancer within the next 3 years of observation. The paper provides a detailed analysis of the electrophysiological characteristics of disorders of neuromuscular transmission, allowing differentiating myasthenia gravis from the LEMS; compared the sensitivity of various immunological and oncologic markers in the early diagnosis of lung tumor; immunohistochemical studies disclosed the possibility to clarify the histological types of lung cancer. Discussed etiologic relationship lung carcinoma and LEMS

Modeling the lexical morphology of Western handwritten signatures.

A handwritten signature is the final response to a complex cognitive and neuromuscular process which is the result of the learning process. Because of the many factors involved in signing, it is possible to study the signature from many points of view: graphologists, forensic experts, neurologists and computer vision experts have all examined them. Researchers study written signatures for psychiatric, penal, health and automatic verification purposes. As a potentially useful, multi-purpose study, this paper is focused on the lexical morphology of handwritten signatures. This we understand to mean the identification, analysis, and description of the signature structures of a given signer. In this work we analyze different public datasets involving 1533 signers from different Western geographical areas. Some relevant characteristics of signature lexical morphology have been selected, examined in terms of their probability distribution functions and modeled through a General Extreme Value distribution. This study suggests some useful models for multi-disciplinary sciences which depend on handwriting signatures.

The Effects of Incline and Level-Grade High-Intensity Interval Treadmill Training on Running Economy and Muscle Power in Well-Trained Distance Runners

Despite a paucity of evidence, uphill running has been touted as a sport-specific resistance-to-movement training tactic capable of enhancing metabolic, muscular, and neuromuscular processes in distance runners in ways similar to previously established resistance-to-movement training methods, such as heavy and/or explosive strength training and plyometric training. Therefore, the purpose of this investigation included documenting the effects of incline and level-grade interval treadmill training on indices of running economy (RE) (i.e., oxygen consumption [VO2] and blood lactate [BLa] responses of submaximal running) and muscle power. Thirty-two well-trained distance runners (age, 27.4 ± 3.8 years; body mass, 64.8 ± 8.9 kg; height, 173.6 ± 6.4 cm; and VO2max, 60.9 ± 8.5 ml·min(-1)·kg(-1)) received assignment to an uphill (GHill = 12), level-grade (GFlat = 12), or control (GCon = 8) group. GHill and GFlat completed 12 interval and 12 continuous run sessions over 6 weeks, whereas GCon maintained their normal training. Dependent variables measured before and after training were VO2 and BLa at 2 separate velocities associated with lactate threshold (VLT) (VO2-60% and VO2-80%; and BLa-60% and BLa-80%, respectively); percentage of VO2max at lactate threshold (%VO2max at VLT); muscle power as assessed through a horizontal 5-jump test (5Jmax); and isokinetic knee extension and flexion at 3 angular velocities (90, 180, and 300°·s(-1)). Statistical significance was set to p ≤ 0.05. All groups significantly improved 5Jmax, VO2-60%, VO2-80%, BLa-60%, and BLa-80%. Additionally, GHill and GFlat significantly improved %VO2max at VLT. Other indices of RE and muscle power did not improve. We conclude incline treadmill training effective for improving the components of RE, but insufficient as a resistance-to-movement exercise for enhancing muscle power output.

Dysphagia Due to Inclusion Body Myositis

This report aimed to present a case of inclusion body myositis presenting with dysphagia and to review the literature. Case report and literature review. Inclusion body myositis is a chronic progressive acquired myopathy, uniquely distinguished by its selective muscle involvement, normal or moderately elevated muscle enzyme concentrations, and a progressive corticosteroid-resistant course. Compared to other inflammatory myopathies, the esophagus is the most commonly involved organ. Specifically, upper esophageal sphincter dysfunction often occurs. Dysphagia may be the only symptom at the time of presentation. Unlike other inflammatory myopathies, dysphagia in inclusion body myositis is steroid resistant. Management can be difficult. The otolaryngologist must consider underlying neuromuscular processes when evaluating the patient presenting with oropharyngeal dysphagia.

Customizing the palatal contour of a complete denture using a Palatogram in a case of partial glossectomy

Our ability to speak is the result of a learned, habitual, neuromuscular process. Speech is a sophisticated, autonomous, unconscious activity. Its production involves neural, muscular, mechanical, aerodynamic, acoustic and auditory factors. Markedly slow and weak speech may result from a weakened physical condition and may indicate a need for complete medical examination. An improperly fabricated oral prosthesismaymodify speech due to the following reasons

106. Combined Electroneurographic and Muscular ultrasound study in healthy neonatal and adult-juvenile populations: Maturational aspects

We used combined Electroneurography and Muscular-UltraSound study (c-ENG-MUS) to evaluate the morpho-functional neuromuscular aspects in healthy neonatal and adult-juvenile populations. The Tibial Anterior muscle was evaluated in 17 neonates, 10 Full-terms (38–40 ws)/ 7 preterms (32–36 ws) and in 11 young adults (19–45 ys) by c-ENG-MUS, measuring: (1) Onset-Peak (OP) and peak-to-peak (PP) amplitudes of maximum Motor-Compound-Action-Potential (mCMAP); (2) maximum Muscular Thickness (mMT); (3) MT at mCMAP’s detection point (mCMAP-MT). In preterms we performed serial studies until the term-age. (Study approved by the Local-Ethics-Committee). In newborns the OP- and PP-mCMAP amplitudes didn’t correlate linearly, unlike the adults; in the newborns’ and adults’ populations the mCMAP-MT and mMT values linearly relate. In newborns, the mCMAP’s amplitude and MT’s absolute value were about half of the adults’ ones. The detection points of mCMAP and mMT didn’t correspond. In preterms the values of mCMAP-amplitude and mMT proportionally increased to the postconceptional-age. The values of mCMAP-amplitude, mMT and mCMAP-MT significantly differed in neonates (full-terms and preterms) respect the adults because of the effect of age. There was no correlation between the mCMAP-amplitude and mMT (no significant site-effect). c-ENG-MUS is a quiclky and easy technique to evaluate the neuromuscular functional and morphological maturational processes.

Neuromuscular induced phonation in a human ex vivo perfused larynx preparation

Considering differences in laryngeal anatomy, degree of control, and range of voice qualities between animals and humans, investigations of the neuromuscular process of voice control are better conducted using a living human larynx in which parametric stimulation of individual laryngeal muscles is possible. Due to difficulties in access and monitoring of laryngeal muscle activities, such investigations are impossible in living human subject experiments. This study reports the recent success in developing an ex vivo perfused human larynx model, which allows parametric muscle stimulation and observation of its influence on phonation of a virtually living human larynx in a well-controlled laboratory environment.

Controversies in Vitamin D Recommendations and Its Possible Roles in Nonskeletal Health Issues

This article discusses one of the current most controversial nutrition topics. Recent vitamin D recommendations, as well as the serum 25-hydroxyvitamin D (25OHD) concentrations and implications on health status are reviewed. The various functions of vitamin D, starting from the cellular level, through autoimmune diseases, cancer, cardiovascular disease, and neuromuscular processes, to its role in obesity and metabolic syndrome, as well as in pregnancy outcomes, are also discussed. The most up-to-date literature published in peer-review scientific journals was reviewed. While the role of vitamin D in bone metabolism and the amount to support bone health is unequivocal, its benefits and/or roles in various other health conditions and the best way to achieve and maintain optimal levels are still controversial. Opinions vary on the recommended intake for vitamin D and what the desirable serum levels of vitamin D may be. Despite the numerous reports about its impact in autoimmune processes, several cancers, cardiovascular diseases, obesity, metabolic syndrome, and pregnancy complications, the evidence is not robust enough to draw definite conclusions or to establish a causal relationship. Only the role of vitamin D in neuromuscular functions and prevention of falls in frail elderly seems to be more substantiated. Reaching the current or even higher levels of consumption (e.g. 1500-2000 IU/day) seems improbable by food and sun exposure only and supplementation should be in place, particularly for individuals at risk, including breast-fed infants, children, pregnant/lactating women, elderly, obese and individuals with fat mal absorption.

Adaptive Fractal Analysis Reveals Limits to Fractal Scaling in Center of Pressure Trajectories

Fractal time series analysis methods are commonly used for analyzing center of pressure (COP) signals with the goal of revealing the underlying neuromuscular processes for upright stance control. The use of fractal methods is often coupled with the assumption that the COP is an instance of fractional Gaussian noise (fGn) or fractional Brownian motion (fBm). Our purpose was to evaluate the applicability of the fGn-fBm framework to the COP in light of several characteristics of COP signals revealed by a new method, adaptive fractal analysis (AFA). AFA quantifies how the variance of the residuals to fits of a globally smooth trend signal scales with the time scale at which the fits are performed. Application of AFA to COP signals revealed that there are potentially three fractal scaling regions in the COP as opposed to one as expected from a pure fGn or fBm process. The scaling region at the fastest scale was anti-persistent and spanned ~30-90 ms, the intermediate was persistent and spanned ~200 ms-1.9 s, and the slowest was anti-persistent and spanned ~5-40 s. The intermediate fractal scaling region was the most clearly defined, but it only contributed around 11% of the total spectral energy of the COP signal, indicating that other features of the COP signal contribute more importantly to the overall dynamics. Also, more than half of the Hurst exponents estimated for the intermediate region were greater than the theoretically expected range [0,1] for fGn-fBm processes. These results suggest the fGn-fBm framework is not appropriate for modeling COP signals. ON-OFF intermittency might provide a better modeling framework for the COP, and multiscale approaches may be more appropriate for analyzing COP data.

The effect of increasing external degrees of freedom on force production and neuromuscular stabilisation

Evidence suggests that during interaction with different environmental dynamics the necessity to stabilise the involved joints leads to altered efficiency in force transmission to the surroundings and a specific orchestration of motor control strategies. However, little is known about the modalities of the changes associated with altered environmental dynamics. In 29 healthy participants, electromyographic (EMG) signals from four muscles of the right leg (M. peroneus longus, M. tibialis anterior, M. vastus medialis, M. gastrocnemius medialis) and three dimensions of force (Fx, Fy, Fz) were recorded. The participants were to exert force against an external object by performing a unilateral leg extension task with the task being influenced by either 0, 1 or 3 mechanical degrees of freedom. We hypothesised that the ankle stabilising muscles would increase their activities with increasing degrees of freedom (DoF), and that increasing external degrees of freedom results in decreased muscle force exerted during the movement task. The progressive change in the type of mechanical interaction from stable to unstable caused a loss of the ability to apply force in movement direction (Fz) which was accompanied by a reduction of Fy and Fx force dimensions. These reductions corresponded to maximum losses of 23% for Fz, 33% for Fx and 41% for Fy in the three degrees of freedom condition (all P < 0.001). Next, the individual muscles showed specific tuning effects, depending on the type of mechanical interaction. Our results suggest that the loss of the ability to exert force effectively against the external object is due to the neuromuscular stabilisation process of the involved joints. The change of the degrees of freedom conditions allowed for assessment of movement- or stabilisation-related adjustments of the motor system.

Inpatient EMG Studies. Do They Help with Patient Care? (P01.197)

Objective: To assess the usage and clinical impact of inpatient electromyography (IP-EMG) studies at a university-based hospital. Background Nerve conduction and electromyography studies are increasingly performed in the inpatient setting. Portable machines and dedicated teams have facilitated this increase. However, the impact of IP-EMG studies on patient care has not been studied. Design/Methods: We retrospectively reviewed the medical records of all patients who had IP-EMG between July 2009 and September 2011 by a single neuromuscular medicine-trained neurologist. Demographic data, results of the study, pre-study clinical impression and post-study diagnostic evaluation and management were analyzed. Results: During the study period, 122 patients underwent 137 IP-EMG studies. Mean age was 53 years and female: male ratio was 1.7:1. Thirteen studies were in patients in an intensive care unit; 6 had either critical illness neuropathy or myopathy. A predominant neurogenic etiology was found in 84 patients. Of these, 8 had acute inflammatory demyelinating polyneuropathy (AIDP) and 42 had chronic axonal neuropathy. Seven patients were newly diagnosed with motor neuron disease following IP-EMG. Twenty patients were classified as radiculopathy or plexopathy. Four patients were diagnosed with non-AIDP acute neuropathies and six patients were diagnosed with inflammatory or toxic myopathy. Twenty-nine IP-EMGs were normal. Seven of 8 AIDP patients had cerebrospinal fluid analysis; all were treated with IVIG and/or plasma exchange. All 6 patients with new onset myopathy had a muscle biopsy after IP-EMG. IP-EMG confirmed the pre-test clinical impression in 67 patients. In the majority of cases where IP-EMG was not confirmatory, the study helped to focus further diagnostic evaluation or led to the conclusion of a non-neurological cause of symptoms. The most common incidental finding judged unrelated to the clinical presentation was median mononeuropathy at the wrist. Conclusions: This study demonstrates that IP-EMG contributes value to clinical decision making for hospitalized patients suspected to have acute neuromuscular processes. Disclosure: Dr. Samuel has nothing to disclose. Dr. Muppidi has nothing to disclose. Dr. Wolfe has received personal compensation for activities with Eli Lilly & Company, Talecris and Genzyme Corporation as a speaker and/or participant on an advisory board.

Temperature Dependency in Motor Skill Learning

ABSTRACT The present study investigated the role of temperature as a contextual condition for motor skill learning. Precision grip task training occurred while forearm cutaneous temperature was either heated (40–45 °C) or cooled (10–15 °C). At test, temperature was either reinstated or changed. Performance was comparable between training conditions while at test, temperature changes decreased accuracy, especially after hot training conditions. After cold training, temperature change deficits were only evident when concurrent force feedback was presented. These findings are the first evidence of localized temperature dependency in motor skill learning in humans. Results are not entirely accounted for by a context-dependent memory explanation and appear to represent an interaction of neuromuscular and sensory processes with the temperature present during training and test.

Immune Response and Mitochondrial Metabolism Are Commonly Deregulated in DMD and Aging Skeletal Muscle

Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors.