Structural and bioenergetic changes in muscle tissue in idiopathic muscular dystonia

Abstract

BACKGROUND. Muscular dystonia is a syndrome with localization of the pathological process in the central nervous system and the formation of local muscle hypertonicity. It is relevant to study changes in the muscles involved in hyperkinesis in dystonia as one of the possible symptoms of the disease.

AIM. To identify structural and bioenergetic changes in muscles in patients with idiopathic muscular dystonia.

MATERIAL AND METHODS. 10 patients were examined with a diagnosis of idiopathic segmental and generalized dystonia, including cervical dystonia syndrome. The control group included 5 conditionally healthy individuals. All patients received injections of botulinum toxin type A with a TWSTRS and Tsui efficacy score before injection and 3 weeks after injection. Structural changes in the muscles were assessed by magnetic resonance imaging (MRI) (1.5 Tl). To assess bioenergetic changes, the parameters of mitochondrial respiration were studied, including basal respiration during oxidation of substrates (pyruvate and pyruvate-malate), respiration during oxidative phosphorylation with various participation of respiratory chain complexes, electron transport chain capacity (ETC), ATP-associated respiration in a trapezius muscle biopsy.

RESULTS. Bioenergetic changes in muscle tissue were revealed in the form of a decrease in the indices of initial respiration, basal respiration with the participation of the I complex (KI) ETC in the process of oxidation of pyruvate and pyruvate-malate substrates, oxidative phosphorylation with the participation of KI. Structural changes of muscle tissue in the form of asymmetric hypertrophy and partial fat replacement of the involved muscles are demonstrated. The presence of fat replacement reduced the difference on the TWSTRS scale before botulinum therapy and 3 weeks after injection.

CONCLUSIONS. Patients with dystonia have bioenergetic changes in muscle tissue in the form of a defect in the work of the KI respiratory chain, but these changes do not affect the effectiveness of botulinum therapy. Structural changes in the form of partial fat replacement of muscle tissue reduce the effectiveness of botulinum therapy.

Keywords

dystonia / mitochondrial dysfunction / the effectiveness of botulinum therapy / structural changes in dystonia / bioenergetic changes in dystonia

References

[1] Albanese A, Bhatia K, Bressman SB et al. Phenomenology and classification of dystonia: A consensus update. Mov Disord. 2013;28(7):863–873. DOI: 10.1002/mds.25475.

[2] Albanese A., Bhatia K., Bressman S.B. et al. Phenomenology and classification of dystonia: A consensus update // Mov. Disord. 2013. Vol. 28. N. 7. P. 863–873. DOI: 10.1002/mds.25475.

[3] Jinnah HA, Sun YV. Dystonia genes and their biological pathways. Neurobiol Dis. 2019;129:159–168. DOI: 10.1016/j.nbd.2019.05.014.

[4] Jinnah H.A., Sun Y.V. Dystonia genes and their biological pathways // Neurobiol. Dis. 2019. Vol. 129. P. 159–168. DOI: 10.1016/j.nbd.2019.05.014.

[5] Chen HX, Tang SP, Gao FT et al. Fibrosis, adipoge-nesis, and muscle atrophy in congenital muscular torticollis. Medicine (Baltimore). 2014;93(23):e138. DOI: 10.1097/MD.0000000000000138.

[6] Chen H.X., Tang S.P., Gao F.T. et al. Fibrosis, adipogenesis, and muscle atrophy in congenital muscular torticollis // Medicine (Baltimore). 2014. Vol. 93. N. 23. P. e138. DOI: 10.1097/MD.0000000000000138.

[7] Jiang B, Zu W, Xu J et al. Botulinum toxin type A relieves sternocleidomastoid muscle fibrosis in congenital muscular torticollis. Int J Biol Macromol. 2018;112:1014–1020. DOI: 10.1016/j.ijbiomac.2018.02.077.

[8] Jiang B., Zu W., Xu J. et al. Botulinum toxin type A relieves sternocleidomastoid muscle fibrosis in congenital muscular torticollis // Int. J. Biol. Macromol. 2018. Vol. 112. P. 1014–1020. DOI: 10.1016/j.ijbiomac.2018.02.077.

[9] Zhang X, Lan D, Ning S et al. Botulinum toxin type A prevents the phenotypic transformation of fibroblasts induced by TGF-β1 via the PTEN/PI3K/Akt signaling pathway. Int J Mol Med. 2019;44(2):661–671. DOI: 10.3892/ijmm.2019.4226.

[10] Zhang X., Lan D., Ning S. et al. Botulinum toxin type A prevents the phenotypic transformation of fibroblasts induced by TGF-β1 via the PTEN/PI3K/Akt signaling pathway // Int. J. Mol. Med. 2019. Vol. 44. N. 2. P. 661–671. DOI: 10.3892/ijmm.2019.4226.

[11] Hao R, Li Z, Chen X, Ye W. Efficacy and possible mechanisms of Botulinum Toxin type A on hypertrophic scarring. J Cosmet Dermatol. 2018;17(3):340–346. DOI: 10.1111/jocd.12534.

[12] Hao R., Li Z., Chen X., Ye W. Efficacy and possible mechanisms of Botulinum Toxin type A on hypertrophic scarring // J. Cosmet. Dermatol. 2018. Vol. 17. N. 3. P. 340–346. DOI: 10.1111/jocd.12534.

[13] Zhang S, Li K, Yu Z et al. Dramatic effect of botulinum toxin type A on hypertrophic scar: A promising therapeutic drug and its mechanism through the SP-NK1R pathway in cutaneous neurogenic inflammation. Front Med (Lausanne). 2022;9:820817. DOI: 10.3389/fmed.2022.820817.

[14] Zhang S., Li K., Yu Z. et al. Dramatic effect of botulinum toxin type A on hypertrophic scar: A promising therapeutic drug and its mechanism through the SP-NK1R pathway in cutaneous neurogenic inflammation // Front. Med. (Lausanne). 2022. Vol. 9. P. 820817. DOI: 10.3389/fmed.2022.820817.

[15] Benecke R, Strümper P, Weiss H. Electron transfer complex I defect in idiopathic dystonia. Ann Neurol. 1992;32(5):683–686. DOI: 10.1002/ana.410320512.

[16] Benecke R., Strümper P., Weiss H. Electron transfer complex I defect in idiopathic dystonia // Ann. Neurol. 1992. Vol. 32. N. 5. P. 683–686. DOI: 10.1002/ana.410320512.

[17] Reichmann H, Naumann M, Hauck S, Janetzky B. Respiratory chain and mitochondrial deoxyribonucleic acid in blood cells from patients with focal and generalized dystonia. Mov Disord. 1994;9(6):597–600. DOI: 10.1002/mds.870090603.

[18] Reichmann H., Naumann M., Hauck S., Janetzky B. Respiratory chain and mitochondrial deoxyribonucleic acid in blood cells from patients with focal and generalized dystonia // Mov. Disord. 1994. Vol. 9. N. 6. P. 597–600. DOI: 10.1002/mds.870090603.

[19] Schapira AH, Warner T, Gash MT et al. Complex I function in familial and sporadic dystonia. Ann Neurol. 1997;41(4):556–559. DOI: 10.1002/ana.410410421.

[20] Schapira A.H., Warner T., Gash M.T. et al. Complex I function in familial and sporadic dystonia // Ann. Neurol. 1997. Vol. 41. N. 4. P. 556–559. DOI: 10.1002/ana.410410421.

[21] Doerrier C, Garcia-Souza LF, Krumschnabel G et al. High-resolution fluorespirometry and OXPHOS protocols for human cells, permeabilized fibers from small biopsies of muscle, and isolated mitochondria. Methods Mol Biol. 2018;1782:31–70. DOI: 10.1007/978-1-4939-7831-1_3.

[22] Doerrier C., Garcia-Souza L.F., Krumschnabel G. et al. High-resolution fluorespirometry and OXPHOS protocols for human cells, permeabilized fibers from small biopsies of muscle, and isolated mitochondria // Methods. Mol. Biol. 2018. Vol. 1782. P. 31–70. DOI: 10.1007/978-1-4939-7831-1_3.

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