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European Journal of Translational Myology logoLink to European Journal of Translational Myology
. 2020 Nov 17;30(4):9437. doi: 10.4081/ejtm.2020.9437

30 Years of Translational Mobility Medicine: 2020 Padua Muscle Days go virtual from Euganean Hills, November 19th to 21st

Ugo Carraro 1,2,✉
PMCID: PMC7844408  PMID: 33520146

Abstract

In the autumn of 2019, the 2020 Padua Muscle Days (PMDs) were planned to be held from March 18 to March 21, 2020. The program listed Scientific Sessions to occur over three full days at either Padova University or the Hotel Augustus on Euganei Hills (Padova), Italy. Abruptly, however, in early January the Coronavirus COVID-19 outbreak started in China and changed the world perspectives. In Italy, the epidemia had the first Italian cases and victims in an area south of Milan and in a Village of the Euganei Hills (Vo Euganeo, Padova). Thus, it was a mandatory decision to post-pone the PMDs meeting to 19-21 November, 2020. Luckily, almost all chairs, speakers, and attendees accepted the decision and have assured their presence in late November by long-distance communications. Thus, the Collection of Abstracts were e-published in 30(1) 2020 Issue of the European Journal of Translational Myology (EJTM) together with the many EJTM Communications submitted by speakers and attendees of the 2020 PMDs Here we add a few new entries and the detailed Program of the 2020 Virtual PMDs to be organized November 19-21, 2020 from the Hotel Petrarca of Euganei Hills (Padova), Italy. The Program of the 2020 Virtual PMDs ends with invitation by Zipora Yablonka-Reuveni and myself to the 2021 (Virtual) Padua Muscle Days, March 25-27, Euganei Hills (Padova), Italy.

Key Words: Translational Myology and Mobility Medicine, COVID-19 in 2020, Padua Muscle Days, Program & New Abstracts

A series of meetings concerning muscle biology, physiology, medicine and rehabilitation, called Padua Muscle Days (PMDs), were initiated more than 30 years ago, specifically to provide experts’ advices on Translational Myology and Mobility Medicine. Always the interest was on implementing basic research and trials to help prevent mobility disorders and/or to manage or rehabilitate young adults and elderly persons suffering from mobility disorders. Thus, the organizers of the 2020 PMDs implemented an intense program to be held from March 18 to March 21, 2020 either in Padova University or in the Hotel Augustus on Euganei Hills (Padova), Italy.1 Abruptly, however, the Coronavirus COVID-19 outbreak, quickly spread and changed the world perspectives. In Italy the virus was first detected in Lombardy and VenetoW within a week, the COVID-2019 affected the first Italian victims in an area south of Milan and in a village of the Euganei Hills (Vo Euganeo, Padova). The village was immediately quarantined, but it was too late. The virus was spreading through the area. Thus, the PMDs was post-poned to 19-21 November, 2020, and the only option was to reprogram the list of presentations of the 2020 PMDs by long-distance communication to maintain international relations when the epidemia worsened again in Autumn. Luckily, chairs, speakers and attendees accepted the decision and have assured their virtual presence. The changes in the PMDs November 19-21 Program are the new dates and a reorganized schedule of the eight Sessions to allow, a world-wide attendance, to follow the Sessions during their mornings or afternoons. The Collection of Abstracts was e-published in the 30(1) 2020 Issue of the European Journal of Translational Myology together with the many EJTM Communications submitted by Speakers and Attendees of the 2020PMDs.1 Here we list, beside a few new Abstracts, the updated Program of the 2020 Virtual PMDs to be held November 19-21, 2020 from the Hotel Petrarca of Euganei Hills (Padova), Italy. The last Virtual Presentation will be invitation by Zipora Yablonka-Reuveni and myself to the 2021 (Virtual) Padua Muscle & Mobility Medicine Days (2021 V-PM3Ds), March 25-27, Euganei Hills (Padova), Italy.

Acknowledgments

The authors thank Attendees for supporting the postpone 2020 Virtual PMDs to 19-21 November, 2020.

List of acronyms

AD

Alzheimer’s disease

CEUs

Calcium Entry Units

CIM

Critical Illness Myopathy

CIP

Critical Illness Polyneuropathy

CMAP

Compound muscle action potential

COVID

Coronavirus COVID-19 outbreak

DMD

Duchenne Muscular Dystrophy

EHSs

Exertional/Environmental Heat Strokes

EJTM

European Journal Translational Myology

GWAS

genome-wide-association studies

ICU

intensive care unit

ICUAW

Intensive Care Unit Acquired Muscle Weakness

LEF

lower extremity function

NTRA

nonlinear trimodal regression analysis

PA

physical activity

PMDs

Padua Muscle Days

SOCE

Store-Operated Ca2+ Entry

SR

sarcoplasmic reticulum

Te

testosterone

TTs

transverse tubules

PM3Ds

Padua Muscle & Mobility Medicine Days

Funding Statement

Funding E-publishing of this typescript is supported by the Armando & Carmela Mioni-Carraro Foundation for Translational Myology Padova, Italy and by PAGEpress, Pavia, Italy. The 2020 Virtual PMDs events are supported by Osato Research Institue, Gifu, Japan, OROBOROS, Insbruck, Austria, Physiko- & Rheuma-therapie, Institute for Physical Medicine and Rehabilitation, St. Pölten, Austria, Centre of Active Ageing—Competence Centre for Health, Prevention and Active Ageing, St. Pölten, Austria and Ludwig Boltzmann Institute for Rehabilitation Research, St. Pölten, Austria.

References

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  • 18.Marrero HG, Stalberg EV. Optimizing testing methods and collection of reference data for differentiating critical illness polyneuropathy from critical illness myopathy. Muscle Nerve 2016;53:555-63. doi: 10.1002/mus.24886 [DOI] [PubMed] [Google Scholar]
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  • 20.Stibler H, Edström L, Ahlbecket K, et al. Electrophoretic determination of the myosin/actin ratio in the diagnosis of critical illness myopathy. Intensive Care Med 2003;29: 1515-27. doi: 10.1007/s00134-003-1894-9 [DOI] [PubMed] [Google Scholar]
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Eur J Transl Myol. 2020 Nov 17;30(4):9437.

2020 Virtual PMDs 19-21 Nov: New entries

The DLK1-DIO3 cluster miRNAs regulate mitochondrial functions in the dystrophic muscle in DMD

Ai Vu Hong 1, Nathalie Bourg 1, Peggy Sanatine 1, Jerome Poupiot 1, Karine Charton 1, Evelyne Gicquel 1, Marco Spinazzi 2, Isabelle Richard 1, David Israeli 1,*

Duchenne Muscular Dystrophy (DMD) is a muscle disease which is caused by the lack of dystrophin expression. MicroRNA profiling in DMD patients and animal models revealed a coordinated dysregulation of clustered miRNAs of the DLK1-DIO3 locus (DD-miRNAs), in both serum and muscles.1,2. DD-miRNA dysregulation was controled epigenetically by DNA and histone methylation of key regulatory elements. A bioinformatics analysis predicted that DD-miRNAs may regulate mitochondrial functions. Indeed coinsedently with DD-miRNA dysregulation, we observed mitochondrial perturbations in the dystrophic muscles. In vivo overexpression of DD-miRNAs in healthy muscles recapitulated these mitochondrial perturbation. Thus, the present study provide evidences for a novel mechanism of mitochondrial dysfunction in DMD

References

  • 1.Jeanson-Leh L, Lameth J, Krimi S, et al. Serum Profiling Identifies Novel Muscle miRNA and Cardiomyopathy-Related miRNA Biomarkers in Golden Retriever Muscular Dystrophy Dogs and Duchenne Muscular Dystrophy Patients. Am J Pathol 2014;184:2885–98. doi: 10.1016/j.ajpath.2014.07.021 [DOI] [PubMed] [Google Scholar]
  • 2.Sanson M, Vu Hong A, Massourides E, et al. miR-379 links glucocorticoid treatment with mitochondrial response in Duchenne muscular dystrophy. Sci Rep 2020;10:9139. doi: 10.1038/s41598-020-66016-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
Eur J Transl Myol. 2020 Nov 17;30(4):9437.

Testosterone therapy in Alzheimer’s disease

Vittorio Emanuel Bianchi 1,*

Alzheimer’s disease (AD) is the neurodegenerative disease responsible of the most common form of dementia. Abnormal amyloid-b (Aβ) deposition induces the amyloid plaques formation and consequent degeneration of neurons in the hippocampus, amygdala, and diencephalon. Etiopathology of AD is multifactorial including genetic factors, malnutrition, and diabetes.1 Aging is most important factor in the development of AD, however, sex hormones are largely involved in AD formation. Both 17β-oestradiol and testosterone (Te) exert a protective function on neuron against AD development regulating the Aβ production, transport, and clearance from the brain. In elderly men a low serum Te levels is correlated with a high risk of Alzheimer's disease, while a higher serum level of free Te in males and females plays a protective effect against AD development. In the present study we search systematically the RCT (randomized clinical trials) from year 2000 until now, who investigated the effect of Te on AD and cognitive impairment. We found seventeen RCT reported. The overall studies found that Te therapy improved cognition and memory, however a few did not find any improvement, other a modest improvement of cognition.2 One study found a detrimental effect of Te administration on verbal memory and in median and prefrontal activity, but no test on cognition were done.3 Discrepancies between the studies are due to the different clinical methodology of investigation, time duration of therapy (small number of patients, clinical investigation of dementia, other pathologies as confounding factors). However, the most relevant drawbacks are related to the lacking of determination other hormones, largely involved in the neurotrophic process, such as 17β-estradiol and IGF-1 that are hormones. Further studies with a strong methology are necessary to evaluate the effect of Te in AD therapy.

References

  • 1.Lee JH, Byun MS, Yi D, et al. Sex-specific association of sex hormones and gonadotropins, with brain amyloid and hippocampal neurodegeneration. Neurobiol Aging 2017;58:34-40. doi: 10.1016/j.neur obiolaging.2017.06.005 [DOI] [PubMed] [Google Scholar]
  • 2.Huang G, Wharton W, Bhasin S., et al. , Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial. Lancet Diabetes Endocrinol 2016;4:657-65. doi: 10.1016/S2213-8587(16)30102-4. Epub 2016 Jul 1 [DOI] [PubMed] [Google Scholar]
  • 3.Bianchi VE, Locatelli V, Rizzi L. Neurotrophic and Neuroregenerative Effects of GH/IGF1. Int J Mol Sci 2017;18:2441. doi: 10.3390/ijms18112441 [DOI] [PMC free article] [PubMed] [Google Scholar]
Eur J Transl Myol. 2020 Nov 17;30(4):9437.

Translational Lecture 1. The genetic underpinning of VO2max and trainability

Hans Hoppeler 1,✉

Maximal oxygen consumption (V̇O2max) denotes the reproducible upper limit of oxygen (energy) flux through the respiratory system into skeletal muscle mitochondria that canbe reached during intense exercise with a large muscle mass. A high V̇O2max is a key requisite for success in all endurance sports such as cycling, cross-country skiing or running over longer distances. However, V̇O2max has also been strongly and negatively associated with cardiovascular diseases and all-cause mortality. V̇O2max can vary by more than twofold between untrained, sedentary subjects with a heritability value greater than 50%.1 Trainability for an individual's V̇O2max also varies massively between subjects. Trainability is independent of sedentary V̇O2max with a similarly high heritability as sedentary V̇O2max.2 The high heritability of sedentary V̇O2max and trainability and its importance for athletic performance as well as health has prompted a massive search for its genetic underpinning. Candidate-gene studies, gene-expression studies and genome-wide-association studies (GWAS) have failed to identify a genetic signature of the high V̇ O2max phenotype.3 This may be due to the fact that there are vast multigenetic regulatory networks in skeletal muscle and in other organs that are responsible both for the set-point and the malleability of V̇O2max. Multigenetic phenotypes such as V̇O2max appear to be emergent properties of multiple underlying transcriptomic networks modified by epistasis, the epigenome and the epitranscriptome. This situation is very similar to the situation of the biological organisation of the immunodefence in COVID 19. It is postualted that the wide variability of the susceptibility to COVID 19 is based on a very similar condition and currently defies characterisation. It is unclear whether an artificial intelligence approach on sufficiently large datasets can make reliable predictions on multigenetic phenotypes such as V̇O2max.

References

  • 1.Schutte NM, Nederend I, Hudziak JJ, et al. Twin-sibling study and meta-analysis on the heritability of maximal oxygen consumption. Physiol Genomics 2016;48, 210-9. doi:10.1152/physiolgenomics.00117.2015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Bouchard C, An P, Rice T, et al. Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study. J Appl Physiol 1999;87,1003-8. doi:10.1152/jappl.1999.87.3.1003. [DOI] [PubMed] [Google Scholar]
  • 3.Sarzynski MA, Ghosh S, Bouchard C. Genomic and transcriptomic predictors of response levels to endurance exercise training. J Physiol 2017;595:2931-9. doi:10.1113/JP272559 [DOI] [PMC free article] [PubMed] [Google Scholar]
Eur J Transl Myol. 2020 Nov 17;30(4):9437.

Soft tissue radiodensity, self-reported physical activity, and lower extremity function in the AGES-Reykjavík study

Kyle J Emunds 1,2,3,*, Ozioma C Okonkwo 1,2,3, Sigurdur Sigurdsson 4, Sarah R Lose 1,2,3, Vilmundur Gudnason 4,5, Ugo Carraro 6,7, Paolo Gargiulo 8,9

While prior studies have highlighted associations between physical activity (PA) and lower extremity function (LEF) in the elderly,1 the mechanisms underlying this relationship remain debated.2 Our recent work has realized the quantitative potential of nonlinear trimodal regression analysis (NTRA) parameters in characterizing soft tissue radiodensity changes and their relationship with sarcopenia and aging health in the population-based AGES-Reykjavík study.3-5 For the present investigation, a series of prospective multivariate regression models were assembled to interrogate whether these soft tissue NTRA parameters mediate the longitudinal relationship between PA and LEF in AGES-Reykjavík. Elderly volunteer subjects from AGES-Reykjavík underwent Computed Tomography (CT) scans and a battery of four LEF tasks: normal and fastest-comfortable gait speed, timed up-and-go, and isometric leg strength. These data were recorded at two study timepoints separated by approximately five years: AGES-I (n = 3,157) and AGES-II (n = 3,098). AGES-I participants were also given a questionnaire to self-report their frequency of weekly moderate–vigorous PA (PAAGES-I). Covariate-adjusted multivariate multiple regression models were assembled under a mediation analysis framework to test whether NTRA parameters mediated the relationship between PAAGES-I and LEFAGES-II. Models of the five-year longitudinal relationship between PAAGES-I and LEFAGES-II indicated that all four LEF tasks were significantly related to PAAGES-I after adjusting for covariates and controlling for multiple statistical comparisons. Modelling the relationship between PAAGES-I and NTRAAGES-II parameters as theorized mediators indicated muscle amplitude (Nm) and location (μm) as potential mediators of LEF. Finally, adding these two parameters to prior PAAGES-I→LEFAGES-II models resulted in the attenuation of PAAGES-I β coefficients, and bootstrapping confirmed Nm and μm as significant partial mediators. This work altogether presents a novel approach toward clarifying the nature of the relationship between PA and LEF in aging populations. In particular, the identification of Nm and μm as significant partial mediators of the longitudinal relationship between PAAGES-I and LEFAGES-II is strong evidence that PA promotes mobility in aging through the preservation of skeletal muscle quantity and quality.

Fig 1.

Fig 1.

Open in a new tab

Graphical summary of the present work, showing the theorized role of NTRA mediators on the five-year longitudinal relationship between self-reported physical activity and LEF.

References

  • 1.Cruz-Jentoft AJ, Landi F, Schneider SM, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age and ageing 2014;43:748759. doi: 10.1093/ageing/afu115 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Landi F, Marzetti E, Martone AM, et al. Exercise as a remedy for sarcopenia. Curr Opin Clin Nutr Metab Care 2014;17:25-31. doi: 10.1097/MCO.000000000 0000018 [DOI] [PubMed] [Google Scholar]
  • 3.Edmunds KJ, Árnadóttir Í, Gíslason MK, et al. Nonlinear Trimodal Regression Analysis of Radiodensitometric Distributions to Quantify Sarcopenic and Sequelae Muscle Degeneration. Comput Math Methods Med 2016;2016:8932950. doi: 10.1155/2016/8932950 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Edmunds KJ, Gíslason M, Sigurðsson S, et al. Advanced quantitative methods in correlating sarcopenic muscle degeneration with lower extremity function biometrics and comorbidities. PloS One 2018;13:e0193241. doi: 10.1371/journal.pone.019 241 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Ricciardi C, Edmunds KJ, Recenti M, et al. Assessing cardiovascular risks from a mid-thigh CT image: a tree-based machine learning approach using radiodensitometric distributions. Sci rep 2020;10:1-13. doi: 10.1038/s41598-020-59873-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
Eur J Transl Myol. 2020 Nov 17;30(4):9437.

Neurogenic vs. myogenic origin of acquired muscle paralysis in intensive care unit (ICU) patients: Evaluation of different diagnostic methods

Humberto DJ Gonzalez Marrero 1, Erik V Stålberg 2, Gerald Cooray 1, Rebeca Corpeno Kalamgi 3, Yvette Hedström 3, Bo-Michael Bellander 4, Inger Nennesmo 5, Lars Larsson 1,3,6,*

The aquired muscle paralysis associated with modern critical care can be of neurogenic or myogenic origin, yet the distinction of between these origins is hampered by the precision of current diagnostic methods. This has resulted into the pooling of all acquired muscle paralyses, independent on origin into the term Intensive Care Unit Acquired Muscle Weakness (ICUAW). This is unfortunate since the acquired neuropathy (Critical Illness Polyneuropathy, CIP) has slower recovery than the myopathy (Critical Illness Myopathy, CIM), therapies need to target underlying mechanisms and every patient deserves as accurate diagnosis as possible.1 This study aims at evaluating different diagnostic methods in the diagnosis of CIP and CIM in critically ill, immobilized and mechanically ventilated intensive care unit (ICU) patients. ICU patients with acquired quadriplegia in responmse to critical care were included in the study. A total of 142 patients were examined with routine electrophysiological methods, together with biochemical analyses of myosin actin (M:A) ratios of muscle biopsies. In addition, the comparison of evoked EMG response in direct vs. indirect muscle stimulation and histopathological analyses of muscle biopsies were performed in a subset of the patients. ICU patients with quadriplegia were stratified into five groups based on the hallmark of CIM, i.e., preferential myosin loss (myosin:actin ratio, M:A) and classified as severe (M:A< 0.5; n= 12), moderate (0.5≤M:A<1; n= 40), mildly moderate (1≤M:A<1.5; n=49), mild (1.5≤M:A<1.7; n= 24) and normal (1.7≤M:A; n=19). Identical M:A ratios were obtained in the small (4-15 mg) muscle samples using a disposable semiautomatic microbiopsy needle instrument as in the larger (>80 mg) samples obtained with a conchotome instrument. Compound muscle action potential (CMAP) duration was increased and amplitude decreased in patients with preferential myosin loss but deviations from this relationship were observed in numerous patients resulting in only weak correlations between CMAP properties and M:A. Advaned electrophysiological methods measuring refractoriness and comparing CMAP amplitude after indirect nerve vs. direct muscle stimulation are time consuming and did not increase precision compared with conventional electrophysiological measurements in the diagnosis of CIM. Low CMAP amplitude upon indirect vs direct stimulation strongly suggests a neurogenic lesion, i.e., CIP, but this was rarely observed among the patients in this study. Histopathological diagnosis of CIM/CIP based on enzyme-histochemical mATPase stainings were hampered by poor quantitive precision of myosin loss and the impact of pathological findings unrelated to the acute quadriplegia. Conventional electrophysiological methods are valuable in identifying a peripheral origin of quadriplegia in ICU patients, but do not reliably separate between neurogenic vs. myogenic origin of paralysis. The hallmark of CIM, the preferential myosin loss, can be reliable evaluated in the small samples obtained with the microbiopsy instrument. The major advantage of this method is that it is less invasive than conventional muscle biopsies, reducing the risk of bleeding in ICU patients frequenly on anticoagulantia treatment, and it can be repeated multiple times during follow up for monitoring purposes.

References

  • 1.Friedrich O, Reid MB, Van den Berghe G., et al. , The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill. Physiol Rev 2015;95:1025-109. doi: 10.1152/physrev.00028.2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Marrero HG, Stalberg EV. Optimizing testing methods and collection of reference data for differentiating critical illness polyneuropathy from critical illness myopathy. Muscle Nerve 2016;53:555-63. doi: 10.1002/mus.24886 [DOI] [PubMed] [Google Scholar]
  • 3.Larsson L, Li X, Edström L., et al. , Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: mechanisms at the cellular and molecular levels. Crit Care Med 2000;28:34-45. [DOI] [PubMed] [Google Scholar]
  • 4.Stibler H, Edström L, Ahlbecket K, et al. Electrophoretic determination of the myosin/actin ratio in the diagnosis of critical illness myopathy. Intensive Care Med 2003;29: 1515-27. doi: 10.1007/s00134-003-1894-9 [DOI] [PubMed] [Google Scholar]
  • 5.Larsson L, Degens H, Li M, et al. Sarcopenia: Aging-Related Loss of Muscle Mass and Function. Physiol Rev 2019;99:427-511. doi: 10.1152/physrev.00061. 2017 [DOI] [PMC free article] [PubMed] [Google Scholar]
Eur J Transl Myol. 2020 Nov 17;30(4):9437.

Central Myonuclei and denervation markers in Cancer Cachexia

Nissrine Daou 1, Medhi Hassani 1,2,3, Emidio Matos 4, Gabriela Salim De Castro 5, Raquel Galvao Figueredo Costa 5, Marilia Seelaender 5, Viviana Moresi 2,3, Marco Rocchi 6, Sergio Adamo 2,3, Zhenlin Li 1, Onnik Agbulut 1, Dario Coletti 1,2,3,*

An idiopathic myopathy characterized by central nuclei in muscle fibers, a hallmark of muscle regeneration, has been observed in cancer patients. In cancer cachexia skeletal muscle is incapable of regeneration, consequently, this observation remains unaccounted for. In C26-tumor bearing, cachectic mice, we observed muscle fibers with central nuclei in the absence of molecular markers of bona fide regeneration. These clustered, non-peripheral nuclei were present in NCAM-expressing muscle fibers. Since NCAM expression is upregulated in denervated myofibers, we searched for additional makers of denervation, including AchRs, MUSK, and HDAC. This last one being also consistently upregulated in cachectic muscles, correlated with an increase of central myonuclei. This held true in the musculature of patients suffering from gastrointestinal cancer, where a progressive increase in the number of central myonuclei was observed in weight stable and in cachectic patients, compared to healthy subjects. Based on all of the above, the presence of central myonuclei in cancer patients and animal models of cachexia is consistent with motor neuron loss or neuromuscular junction perturbation and could underlie a previously neglected phenomenon of denervation, rather than representing myofiber damage and regeneration in cachexia. Similarly to aging, denervation-dependent myofiber atrophy could contribute to muscle wasting in cancer cachexia..

References

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Eur J Transl Myol. 2020 Nov 17;30(4):9437.

Exercise-activated Ca2+ entry and enhanced risk of Heat Stroke

Barbara Girolami 1, Laura Pietrangelo 1, Antonio Michelucci 1, Matteo Serano 1, Feliciano Protasi 1,*

Exertional/Environmental Heat Strokes (EHSs) are hyperthermic crises triggered by strenuous physical exercise and/or exposure to environmental heat, which are caused by an altered intracellular Ca2+ homeostasis in muscle (Bouchama and Knochel, 2002).1 Store-Operated Ca2+ Entry (SOCE) is a mechanism that influences intracellular Ca2+ levels, allowing recovery of extracellular Ca2+ during prolonged activity. We recently demonstrated that exercise leads to formation of Calcium Entry Units (CEUs), intracellular junctions between stacks of sarcoplasmic reticulum (SR) and transverse tubules (TTs) at the I band that promote interaction between STIM1 and Orai1, the two proteins that mediate SOCE (Boncompagni et al. 2017; Protasi et al. 2020). 2,3 Here we tested the hypothesis that exercise-induced assembly of CEUs may increase the risk of hyperthermic crisis when physical activity is performed in challenging environmental conditions. 4 months old mice were: a) first, divided in 3 experimental groups: control, trained-1m (1 month of voluntary running in wheel cages), and exercised-1h (1 hour of incremental treadmill run); and b) second, subjected to an incremental treadmill run of 45 min at 34°C and 40% humidity. We then: a) measured the internal temperature of mice, which was higher in the pre-exercised groups (trained-1m: 38.9°C ± 0.33; exercised-1h: 38.7°C ± 0.40) compared to control (37.9°C ± 0.17). b) applied an ex-vivo exertional stress protocol to isolated EDL muscles (tetanic stimulation performed at 30°C) and verified that samples from trained-1m and exercised-1h mice generated a tension significantly greater than control. c) Analyzed CEUs by electron microscopy (EM) and verified that EDL muscles of exercised-1h ad trained-1m mice contained a greater number of elements forming CEUs. The data collected suggest that assembly of Calcium Entry Units during exercise could predispose to EHS when exercise is performed in challenging environmental conditions.

References

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