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. 2022 Apr 19;23(9):4483.
doi: 10.3390/ijms23094483.

Effects of Low-Intensity and Long-Term Aerobic Exercise on the Psoas Muscle of mdx Mice: An Experimental Model of Duchenne Muscular Dystrophy

Emilly Sigoli  1 , Rosangela Aline Antão  1 , Maria Paula Guerreiro  1 , Tatiana Oliveira Passos de Araújo  1 , Patty Karina Dos Santos  1 , Daiane Leite da Roza  2 , Dilson E Rassier  3 , Anabelle Silva Cornachione  1
Affiliations

Effects of Low-Intensity and Long-Term Aerobic Exercise on the Psoas Muscle of mdx Mice: An Experimental Model of Duchenne Muscular Dystrophy

Emilly Sigoli et al. Int J Mol Sci. .

Abstract

Duchenne muscular dystrophy (DMD) is a muscle disease characterized by the absence of the protein dystrophin, which causes a loss of sarcolemma integrity, determining recurrent muscle injuries, decrease in muscle function, and progressive degeneration. Currently, there is a need for therapeutic treatments to improve the quality of life of DMD patients. Here, we investigated the effects of a low-intensity aerobic training (37 sessions) on satellite cells, peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α protein (PGC-1α), and different types of fibers of the psoas muscle from mdx mice (DMD experimental model). Wildtype and mdx mice were randomly divided into sedentary and trained groups (n = 24). Trained animals were subjected to 37 sessions of low-intensity running on a motorized treadmill. Subsequently, the psoas muscle was excised and analyzed by immunofluorescence for dystrophin, satellite cells, myosin heavy chain (MHC), and PGC-1α content. The minimal Feret's diameters of the fibers were measured, and light microscopy was applied to observe general morphological features of the muscles. The training (37 sessions) improved morphological features in muscles from mdx mice and caused an increase in the number of quiescent/activated satellite cells. It also increased the content of PGC-1α in the mdx group. We concluded that low-intensity aerobic exercise (37 sessions) was able to reverse deleterious changes determined by DMD.

Keywords: Duchenne muscular dystrophy; PGC-1α; immunofluorescence; low-intensity aerobic exercise; mdx mice; satellite cells.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Dystrophin protein immunostaining in the psoas muscle of mice. (A) Wildtype mice (control); dystrophin present in green. (B) mdx mice (dystrophic); dystrophin absent. Cell nuclei were stained with DAPI (blue). Images were obtained with the ImageXpress XLS System microscope at 20× magnification. Scale bar = 100 µm.
Figure 2
Figure 2
Low-intensity exercise improved the morphological characteristics of the dystrophic muscle. (A) Normal cytoarchitecture of the psoas muscle of WT-SED mice. (B) Normal cytoarchitecture of the psoas muscle of WT-TR mice. (C) Pathological changes in the psoas muscle of mdx-SED mice. (D) Exercise improved the tissue cytoarchitecture of mdx-TR mice, although pathological characteristics were still observed. Asterisk: basophilic cell; thick arrow: centralized nucleus; red arrow: necrosis/inflammatory infiltrate; arrowhead: splitting; double arrow: variation in fiber size. Scale bar = 100 µm.
Figure 3
Figure 3
Satellite cell number (Pax7 marker) is increased in dystrophic muscles after 37 sessions of low-intensity exercise. (A) Representative images of immunostaining of quiescent/activated satellite cells through the Pax7 antibody. Laminin (red, Cy5), nuclei (blue, DAPI), and Pax7 (green, FITC) are shown. White arrows: Indication of SCs (Pax7 + underlying nuclei). Images were obtained with the ImageXpress XLS System microscope at 40× magnification. Scale bar = 100 µm (laminin, nuclei, Pax7 and merged panels). All zoomed areas provided better visualization of the SCs (scale bar = 20 µm). SCs were identified by their localization below the laminin superimposed with the nuclei. (B) As expected, the WT-SED group had few quiescent/activated SCs when compared to the mdx-SED group. After a low-intensity training for 37 sessions, the mdx-TR group showed increased SC content when compared to the mdx-SED group. * p < 0.05; ns: not significant. Round symbol: WT-SED; Square symbol: WT-TR; Triangle symbol: mdx-SED; Inverted triangle symbol: mdx-TR. Abbreviations: WT-SED: sedentary wildtype; WT-TR: trained wildtype; mdx-SED: sedentary mdx; mdx-TR: trained mdx.
Figure 4
Figure 4
Myogenin (satellite cells) content is increased in sedentary mdx mice. (A) Representative images of immunostaining of SC in differentiation/fusion through the F5D antibody (myogenin). Laminin (red, Cy5), nuclei (blue, DAPI), and myogenin (green, FITC) are shown. White arrows: Indication of SCs (F5D + underlying nuclei). Images were obtained with the ImageXpress XLS System microscope at 20× magnification. Scale bar = 100 µm (laminin, nuclei, myogenin, and merged panels). All zoomed areas provided better visualization of the SCs (scale bar = 30 µm). SCs were identified by their localization below the laminin superimposed with the nuclei. (B) As expected, the WT-SED group had fewer SCs in differentiation/fusion when compared to the mdx-SED group. * p < 0.05, ns: not significant. Round symbol: WT-SED; Square symbol: WT-TR; Triangle symbol: mdx-SED; Inverted triangle symbol: mdx-TR. Abbreviations: WT-SED: sedentary wildtype; WT-TR: trained wildtype; mdx-SED: sedentary mdx; mdx-TR: trained mdx.
Figure 5
Figure 5
PGC-1α content is increased in dystrophic muscles. (A) Representative images of immunostaining of PGC-1α. Laminin (red, Cy5), nuclei (blue, DAPI), and PGC-1α (green, FITC) are shown. White arrows: Indication of PGC-1α. Images were obtained with the ImageXpress XLS System microscope at 20× magnification. Scale bar = 100 µm. All zoomed areas provided better visualization of the PGC-1α (scale bar = 30 µm). (B) mdx-SED group showed higher expression of PGC-1α when compared to the WT-SED group. After low-intensity training (37 sessions), the WT-TR and mdx-TR groups showed increased expression of PGC-1α when compared to the sedentary animals. * p < 0.05. Round symbol: WT-SED; Square symbol: WT-TR; Triangle symbol: mdx-SED; Inverted triangle symbol: mdx-TR. Abbreviations: WT-SED: sedentary wildtype; WT-TR: trained wildtype; mdx-SED: sedentary mdx; mdx-TR: trained mdx. PGC-1α: Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α protein.
Figure 6
Figure 6
Percentage of type IIA, IIAD/DA, IID, IIDB/BD, and IIB muscle fibers in all groups studied. There was no change in the number of different fiber types. Abbreviations: WT-SED: sedentary wildtype; WT-TR: trained wildtype; mdx-SED: sedentary mdx; mdx-TR: trained mdx.
Figure 7
Figure 7
Representative images of immunostaining of different fiber types. MHC IIB (red, Cy5), nuclei (blue, DAPI), and MHC IIA (green, FITC) are shown. Images were obtained with the ImageXpress XLS System microscope at 4× magnification. Scale bar = 5000 µm (psoas muscle panels). All Zoomed areas at 40× magnification provided better visualization of the types of fibers in the psoas muscle (scale bar = 100 µm). Abbreviations: WT-SED: sedentary wildtype; WT-TR: trained wildtype; mdx-SED: sedentary mdx; mdx-TR: trained mdx.
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References

    1. Dietz A.R., Connolly A., Dori A., Zaidman C.M. Intramuscular blood flow in Duchenne and Becker Muscular Dystrophy: Quantitative power Doppler sonography relates to disease severity. Clin. Neurophysiol. 2020;131:1–5. doi: 10.1016/j.clinph.2019.09.023. - DOI - PMC - PubMed
    1. Santos N.M., Rezende M.D.M., Terni A., Hayashi M.C.B., Fávero F.M., Quadros A.A.J., Reis L.I.O., dos Adissi M., Langer A.L., Fontes S.V., et al. Perfil clínico e funcional dos pacientes com Distrofia Muscular de Duchenne assistidos na Associação Brasileira de Distrofia Muscular (ABDIM) attending the Brazilian Association of muscular dystrophy (ABDIM) Rev. Neurocienc. 2006;14:015–022. doi: 10.34024/rnc.2006.v14.8782. - DOI
    1. Alderton J.M., Steinhardt R.A. Calcium influx through calcium leak channels is responsible for the elevated levels of calcium-dependent proteolysis in dystrophic myotubes. J. Biol. Chem. 2000;275:9452–9460. doi: 10.1074/jbc.275.13.9452. - DOI - PubMed
    1. Le Rumeur E. Dystrophin and the two related genetic diseases, duchenne and becker muscular dystrophies. Bosn. J. Basic Med. Sci. 2015;15:14–20. doi: 10.17305/bjbms.2015.636. - DOI - PMC - PubMed
    1. Arbanas J., Starcevic Klasan G., Nikolic M., Jerkovic R., Miljanovic I., Malnar D. Fibre type composition of the human psoas major muscle with regard to the level of its origin. J. Anat. 2009;215:636–641. doi: 10.1111/j.1469-7580.2009.01155.x. - DOI - PMC - PubMed

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