{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:04Z","timestamp":1785434884949,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"START Grants of RWTH Aachen University Hospital","award":["111\/25"],"award-info":[{"award-number":["111\/25"]}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["202206170014"],"award-info":[{"award-number":["202206170014"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"award":["202206170014"],"award-info":[{"award-number":["202206170014"]}],"id":[{"id":"https:\/\/ror.org\/04atp4p48","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangzhou Panyu Fifth Peoples\u2019 Hospital","award":["440181198912140017"],"award-info":[{"award-number":["440181198912140017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Presynaptic terminals (PTs) in the neuromuscular junction (NMJ) are essential regulators of skeletal muscle function and are responsible for the translation of electrical impulses from motor neurons into muscle contraction. The present exploratory study aimed to compare PT adaptations in spinalis muscle samples from the concave and convex regions of the spine in three cases of advanced scoliosis, which exhibited marked asymmetry in muscle development. Methods: Spinalis muscle sample pairs were retrieved after surgical procedures and subjected to immunofluorescence (IF)-based spatial analysis of PTs, histological assessment of muscle fibers, and expression analyses of inflammatory and neurotrophic proteins. Results: IF images revealed distinct differences in PT parameters between spinalis samples obtained from the corresponding concave and convex sides of spinal deformities. Advanced statistical models revealed a consistent tendency for concave spinalis muscles to develop lower PT numbers, along with decreased expression of relevant components, neurofilament M, and synaptic vesicle glycoprotein 2. Moreover, these impairments were accompanied by increased expression levels of IFN alpha, which has been previously implicated in NMJ disorders, neuropathies, and myopathies. Conclusions: In the concave regions of spinal deformities, continuously compressed spinalis muscles may be particularly susceptible to PT alteration and denervation. However, comprehensive multicenter validation studies are required to better define the relationships among PT alterations, IFN alpha expression, and muscle tissue compression.<\/jats:p>","DOI":"10.3390\/jcm15124532","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T01:52:08Z","timestamp":1781229128000},"page":"4532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Presynaptic Terminal Alterations in Concave and Convex Spinalis Muscles: A Pilot Exploratory Study in Advanced Scoliosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Sebastian L.","family":"Schubert","sequence":"first","affiliation":[{"name":"Clinic for Orthopedics, Trauma, and Reconstructive Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3182-0856","authenticated-orcid":false,"given":"Xiaoying","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanyang","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Clinic for Orthopedics, Trauma, and Reconstructive Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1903-0202","authenticated-orcid":false,"given":"Miguel","family":"Pishnamaz","sequence":"additional","affiliation":[{"name":"Clinic for Orthopedics, Trauma, and Reconstructive Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4102-0748","authenticated-orcid":false,"given":"Mahtab","family":"Nourbakhsh","sequence":"additional","affiliation":[{"name":"Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, S.J., Li, M.X., Ren, J., Tao, J.M., Fang, M., and Kong, L.J. (2025). Global prevalence and associated risk factors of scoliosis in children and adolescents: A systematic review and meta-analysis. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-24905-4"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s43390-024-00904-0","article-title":"Back pain in adolescent idiopathic scoliosis: Frequency and risk factors","volume":"12","author":"Sarkovich","year":"2024","journal-title":"Spine Deform."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1097\/CORR.0000000000000405","article-title":"Classifications in Brief: The Lenke Classification for Adolescent Idiopathic Scoliosis","volume":"476","author":"Slattery","year":"2018","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1169","DOI":"10.1002\/jsp2.1169","article-title":"Paraspinal muscle morphology and composition in adolescent idiopathic scoliosis: A histological analysis","volume":"4","author":"Shahidi","year":"2021","journal-title":"JOR Spine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e70129","DOI":"10.1002\/jsp2.70129","article-title":"Beyond the Curve: The Muscle-Specific Asymmetries of Adolescent Idiopathic Scoliosis","volume":"8","author":"Duncombe","year":"2025","journal-title":"JOR Spine"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chan, R.Y.H., Ma, A.C.F., Cheung, T.S.K., Chan, J.C.L., Kwok, R.W.Y., Fu, A.C.L., and Tsang, S.M.H. (2023). Effect of muscle fatigue of the thoracic erector spinae on neuromuscular control when performing the upper extremity functional tasks in people with adolescent idiopathic scoliosis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0281001"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E1159","DOI":"10.1097\/BRS.0000000000000467","article-title":"Three-Dimensional Characterization of Torsion and Asymmetry of the Intervertebral Discs Vertebral Bodies in Adolescent Idiopathic Scoliosis","volume":"39","author":"Brink","year":"2014","journal-title":"Spine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00586-014-3701-4","article-title":"Idiopathic scoliosis and the vestibular system","volume":"24","author":"Hawasli","year":"2015","journal-title":"Eur. Spine J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pialasse, J.P., Descarreaux, M., Mercier, P., Blouin, J., and Simoneau, M. (2015). The Vestibular-Evoked Postural Response of Adolescents with Idiopathic Scoliosis Is Altered. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143124"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e168783","DOI":"10.1172\/JCI168783","article-title":"Impaired glycine neurotransmission causes adolescent idiopathic scoliosis","volume":"134","author":"Wang","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hong, S., Suh, J.H., Kim, J., Lim, J., Lee, S., Lee, C., Cho, S., Lee, J.C., Lee, J., and Ryu, J.S. (2026). Association Between Asymmetrical Muscle Activation and Three-Dimensional Spinal Deformity in Thoracic-Origin Idiopathic Scoliosis Assessed Using Surface Electromyography and EOS Imaging. J. Clin. Med., 15.","DOI":"10.3390\/jcm15020784"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wu, Q.K., Chen, Z.Q., Chen, K., Li, X., Guo, H.B., Zhou, X.Y., Liang, J.P., and Du, Q. (2026). Neuromorphological Alterations in the Somatosensory System of Adolescent Idiopathic Scoliosis: A Systematic Review of Magnetic Resonance Imaging Studies. Children, 13.","DOI":"10.3390\/children13040499"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liang, Z.Y., Chen, X.Y., and Nourbakhsh, M. (2026). New Insights into Neuromuscular Junction Biology: Evidence from Human and Animal Research. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031253"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"160240","DOI":"10.1098\/rsob.160240","article-title":"NMJ-morph reveals principal components of synaptic morphology influencing structure-function relationships at the neuromuscular junction","volume":"6","author":"Jones","year":"2016","journal-title":"Open Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/jcsm.13173","article-title":"Effects of a 2-year exercise training on neuromuscular system health in older individuals with low muscle function","volume":"14","author":"Monti","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.jmb.2004.08.012","article-title":"Systematic delineation of a calmodulin peptide interaction","volume":"343","author":"Hultschig","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/joa.13260","article-title":"Comparative anatomy of the mammalian neuromuscular junction","volume":"237","author":"Boehm","year":"2020","journal-title":"J. Anat."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liang, Z., Schubert, S.L., Muller, A., Pishnamaz, M., Hildebrand, F., Nourbakhsh, M., and Chen, X. (2026). Spatiotemporal Remodeling of Presynaptic Terminals in Human Neuromuscular Junctions. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27041928"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.toxicon.2022.04.003","article-title":"The distribution of neuromuscular junctions depends on muscle pennation, when botulinum neurotoxin receptors and SNAREs expression are uniform in the rat","volume":"212","author":"Carre","year":"2022","journal-title":"Toxicon"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ohno, K., Ohkawara, B., Shen, X.M., Selcen, D., and Engel, A.G. (2023). Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043730"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e70309","DOI":"10.1111\/ene.70309","article-title":"Beyond the Surface: Investigating the Potential Mechanisms of Non-Motor Symptoms in Myasthenia Gravis","volume":"32","author":"Wang","year":"2025","journal-title":"Eur. J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1358","DOI":"10.1002\/jsp2.1358","article-title":"The morphological discrepancy of neuromuscular junctions between bilateral paraspinal muscles in patients with adolescent idiopathic scoliosis: A quantitative immunofluorescence assay","volume":"7","author":"Zhang","year":"2024","journal-title":"JOR Spine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s12565-009-0013-6","article-title":"Segmental level discrepancy of human iliocostalis muscles and their innervation","volume":"84","author":"Nomizo","year":"2009","journal-title":"Anat. Sci. Int."},{"key":"ref_24","first-page":"323","article-title":"A Note on Location Parameter Estimation using the Weighted Hodges-Lehmann Estimator","volume":"23","author":"Gao","year":"2024","journal-title":"Ind. Eng. Manag. Syst."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00223-025-01473-8","article-title":"The Inflammation-Energy Metabolism Axis: A Central Driver of Sarcopenia-Osteoporosis: A Narrative Review","volume":"117","author":"Jiang","year":"2026","journal-title":"Calcif. Tissue Int."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sun, D., Ding, Z.H., Hai, Y., and Cheng, Y.Z. (2023). Advances in epigenetic research of adolescent idiopathic scoliosis and congenital scoliosis. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1211376"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Stansberry, W.M., and Pierchala, B. (2023). Neurotrophic factors in the physiology of motor neurons and their role in the pathobiology and therapeutic approach to amyotrophic lateral sclerosis. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1238453"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jneuroim.2008.12.008","article-title":"Interferon alpha and neuromuscular disorders","volume":"207","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1113\/JP280679","article-title":"Influence of sex on the age-related adaptations of neuromuscular function and motor unit properties in elite masters athletes","volume":"599","author":"Piasecki","year":"2021","journal-title":"J. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/ejn.13059","article-title":"Lack of motor recovery after prolonged denervation of the neuromuscular junction is not due to regenerative failure","volume":"43","author":"Sakuma","year":"2016","journal-title":"Eur. J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1111\/joa.13463","article-title":"Small junction, big problems: Neuromuscular junction pathology in mouse models of amyotrophic lateral sclerosis (ALS)","volume":"241","author":"Alhindi","year":"2022","journal-title":"J. Anat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"713519","DOI":"10.1155\/2013\/713519","article-title":"Interferon alpha association with neuromyelitis optica","volume":"2013","author":"Asgari","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00296-020-04735-w","article-title":"Inflammatory milieu of muscle biopsies in juvenile dermatomyositis","volume":"41","author":"Sag","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S124","DOI":"10.1016\/j.otsr.2012.11.002","article-title":"Neuromuscular scoliosis","volume":"99","author":"Vialle","year":"2013","journal-title":"Orthop. Traumatol. Surg. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4532\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T02:18:02Z","timestamp":1781230682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":34,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["jcm15124532"],"URL":"https:\/\/doi.org\/10.3390\/jcm15124532","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]}}}