{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:13:23Z","timestamp":1788282803256,"version":"build-2803163510"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008678","name":"Universit\u00e4t Leipzig","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008678","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Motor neuron (MN) loss is a hallmark of neurodegenerative disorders, yet its assessment remains variable, confounding mechanistic and therapeutic interpretation. To address this, we conducted a systematic review and meta-analysis of spinal muscular atrophy (SMA) mouse studies, revealing 60% variability in reported MN loss, for which spinal cord sampling emerged as a major contributor. Using a whole-segment approach with tissue clearing, MN tracing, and multimodal imaging, we confirmed segment-dependent differences in MN counts. Common MN markers (SMI-32, Nissl) lacked specificity, whereas choline acetyltransferase (ChAT) provided robust labeling in murine and human spinal cords. Deep learning\u2013based whole-mount segmentation enabled unbiased MN quantification and validated manual counts. Integrating analysis with computational modeling established segment sampling as a key driver of variability and revealed degeneration patterns: widespread MN loss in amyotrophic lateral sclerosis (ALS), selective MN loss in severe SMA, and preservation in mild SMA models. These findings establish a framework for reproducible MN quantification.<\/jats:p>","DOI":"10.1186\/s40478-026-02415-7","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:25:42Z","timestamp":1788276342000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases"],"prefix":"10.1186","volume":"14","author":[{"given":"Leonie","family":"Sowoidnich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron L.","family":"Norman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gerstner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiane K.","family":"Siemund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannik M.","family":"Buettner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Pagiazitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Dreilich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Pilz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dajun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte J.","family":"Sumner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Paradis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Z.","family":"Mentis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"2415_CR1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3389\/fncel.2014.00293","volume":"8","author":"N Stifani","year":"2014","unstructured":"Stifani N (2014) Motor neurons and the generation of spinal motor neuron diversity. Front Cell Neurosci 8:293. https:\/\/doi.org\/10.3389\/fncel.2014.00293","journal-title":"Front Cell Neurosci"},{"key":"2415_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2021.120099","volume":"434","author":"R Chaudhary","year":"2022","unstructured":"Chaudhary R, Agarwal V, Rehman M, Kaushik AS, Mishra V (2022) Genetic architecture of motor neuron diseases. J Neurol Sci 434:120099. https:\/\/doi.org\/10.1016\/j.jns.2021.120099","journal-title":"J Neurol Sci"},{"key":"2415_CR3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1093\/bmb\/ldp049","volume":"93","author":"RW Orrell","year":"2010","unstructured":"Orrell RW (2010) Motor neuron disease: systematic reviews of treatment for ALS and SMA. Br Med Bull 93:145\u2013159. https:\/\/doi.org\/10.1093\/bmb\/ldp049","journal-title":"Br Med Bull"},{"key":"2415_CR4","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1679\/aohc.64.461","volume":"64","author":"H Yaginuma","year":"2001","unstructured":"Yaginuma H, Sato N, Homma S, Oppenheim RW (2001) Roles of caspases in the programmed cell death of motoneurons in vivo. Arch Histol Cytol 64:461\u2013474. https:\/\/doi.org\/10.1679\/aohc.64.461","journal-title":"Arch Histol Cytol"},{"key":"2415_CR5","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/S0079-6123(08)60542-7","volume":"102","author":"LJ Houenou","year":"1994","unstructured":"Houenou LJ, Li L, Lo AC, Yan Q, Oppenheim RW (1994) Naturally occurring and axotomy-induced motoneuron death and its prevention by neurotrophic agents: a comparison between chick and mouse. Prog Brain Res 102:217\u2013226. https:\/\/doi.org\/10.1016\/S0079-6123(08)60542-7","journal-title":"Prog Brain Res"},{"key":"2415_CR6","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1073\/pnas.042693799","volume":"99","author":"M Celik","year":"2002","unstructured":"Celik M, Gokmen N, Erbayraktar S, Akhisaroglu M, Konakc S, Ulukus C, Genc S, Genc K, Sagiroglu E, Cerami A, Brines M (2002) Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci U S A 99:2258\u20132263. https:\/\/doi.org\/10.1073\/pnas.042693799","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2415_CR7","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1111\/j.1471-4159.2008.05230.x","volume":"105","author":"NA Prow","year":"2008","unstructured":"Prow NA, Irani DN (2008) The inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis. J Neurochem 105:1276\u20131286. https:\/\/doi.org\/10.1111\/j.1471-4159.2008.05230.x","journal-title":"J Neurochem"},{"key":"2415_CR8","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1002\/neu.480250702","volume":"25","author":"L Li","year":"1994","unstructured":"Li L, Oppenheim RW, Lei M, Houenou LJ (1994) Neurotrophic agents prevent motoneuron death following sciatic nerve section in the neonatal mouse. J Neurobiol 25:759\u2013766. https:\/\/doi.org\/10.1002\/neu.480250702","journal-title":"J Neurobiol"},{"key":"2415_CR9","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/sj.sc.3101674","volume":"43","author":"W Xu","year":"2005","unstructured":"Xu W, Chi L, Xu R, Ke Y, Luo C, Cai J, Qiu M, Gozal D, Liu R (2005) Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury. Spinal Cord 43:204\u2013213. https:\/\/doi.org\/10.1038\/sj.sc.3101674","journal-title":"Spinal Cord"},{"key":"2415_CR10","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.ncl.2015.07.005","volume":"33","author":"T Liewluck","year":"2015","unstructured":"Liewluck T, Saperstein DS (2015) Progressive muscular atrophy. Neurol Clin 33:761\u2013773. https:\/\/doi.org\/10.1016\/j.ncl.2015.07.005","journal-title":"Neurol Clin"},{"key":"2415_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.71","volume":"3","author":"O Hardiman","year":"2017","unstructured":"Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH (2017) Amyotrophic lateral sclerosis. Nat Rev Dis Primers 3:17071. https:\/\/doi.org\/10.1038\/nrdp.2017.71","journal-title":"Nat Rev Dis Primers"},{"key":"2415_CR12","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s00415-018-8968-7","volume":"266","author":"M Breza","year":"2019","unstructured":"Breza M, Koutsis G (2019) Kennedy\u2019s disease (spinal and bulbar muscular atrophy): a clinically oriented review of a rare disease. J Neurol 266:565\u2013573. https:\/\/doi.org\/10.1007\/s00415-018-8968-7","journal-title":"J Neurol"},{"key":"2415_CR13","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12040845","author":"S Jablonka","year":"2024","unstructured":"Jablonka S, Yildirim E (2024) Disease mechanisms and therapeutic approaches in SMARD1-insights from animal models and cell models. Biomedicines. https:\/\/doi.org\/10.3390\/biomedicines12040845","journal-title":"Biomedicines"},{"key":"2415_CR14","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.tins.2020.11.009","volume":"44","author":"B Wirth","year":"2021","unstructured":"Wirth B (2021) Spinal muscular atrophy: in the challenge lies a solution. Trends Neurosci 44:306\u2013322. https:\/\/doi.org\/10.1016\/j.tins.2020.11.009","journal-title":"Trends Neurosci"},{"key":"2415_CR15","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1007\/s00109-008-0388-1","volume":"86","author":"LK Tsai","year":"2008","unstructured":"Tsai LK, Tsai MS, Ting CH, Li H (2008) Multiple therapeutic effects of valproic acid in spinal muscular atrophy model mice. J Mol Med (Berl) 86:1243\u20131254. https:\/\/doi.org\/10.1007\/s00109-008-0388-1","journal-title":"J Mol Med (Berl)"},{"key":"2415_CR16","doi-asserted-by":"publisher","first-page":"3906","DOI":"10.1093\/hmg\/ddp333","volume":"18","author":"VB Mattis","year":"2009","unstructured":"Mattis VB, Ebert AD, Fosso MY, Chang CW, Lorson CL (2009) Delivery of a read-through inducing compound, TC007, lessens the severity of a spinal muscular atrophy animal model. Hum Mol Genet 18:3906\u20133913. https:\/\/doi.org\/10.1093\/hmg\/ddp333","journal-title":"Hum Mol Genet"},{"key":"2415_CR17","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1093\/jnen\/nly033","volume":"77","author":"C Cervero","year":"2018","unstructured":"Cervero C, Blasco A, Tarabal O, Casanovas A, Piedrafita L, Navarro X, Esquerda JE, Caldero J (2018) Glial activation and central synapse loss, but not motoneuron degeneration, are prevented by the sigma-1 receptor agonist PRE-084 in the Smn2B\/- mouse model of spinal muscular atrophy. J Neuropathol Exp Neurol 77:577\u2013597. https:\/\/doi.org\/10.1093\/jnen\/nly033","journal-title":"J Neuropathol Exp Neurol"},{"key":"2415_CR18","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1093\/hmg\/ddi078","volume":"14","author":"TT Le","year":"2005","unstructured":"Le TT, Pham LT, Butchbach ME, Zhang HL, Monani UR, Coovert DD, Gavrilina TO, Xing L, Bassell GJ, Burghes AH (2005) SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum Mol Genet 14:845\u2013857. https:\/\/doi.org\/10.1093\/hmg\/ddi078","journal-title":"Hum Mol Genet"},{"key":"2415_CR19","doi-asserted-by":"publisher","first-page":"4494","DOI":"10.1093\/hmg\/ddw278","volume":"25","author":"M Eshraghi","year":"2016","unstructured":"Eshraghi M, McFall E, Gibeault S, Kothary R (2016) Effect of genetic background on the phenotype of the Smn2B\/- mouse model of spinal muscular atrophy. Hum Mol Genet 25:4494\u20134506. https:\/\/doi.org\/10.1093\/hmg\/ddw278","journal-title":"Hum Mol Genet"},{"key":"2415_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103376","volume":"24","author":"JM Buettner","year":"2021","unstructured":"Buettner JM, Sime Longang JK, Gerstner F, Apel KS, Blanco-Redondo B, Sowoidnich L, Janzen E, Langenhan T, Wirth B, Simon CM (2021) Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models. iScience 24:103376. https:\/\/doi.org\/10.1016\/j.isci.2021.103376","journal-title":"iScience"},{"key":"2415_CR21","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/B978-0-12-374247-6.50020-1","volume-title":"The spinal cord","author":"CGP Watson","year":"2009","unstructured":"Watson CGP, Kayalioglu G, Heise C (2009) Chapter 16 - Atlas of the mouse spinal cord. The spinal cord. Academic Press, pp 308\u2013379. https:\/\/doi.org\/10.1016\/B978-0-12-374247-6.50020-1"},{"key":"2415_CR22","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.cell.2008.06.019","volume":"134","author":"JS Dasen","year":"2008","unstructured":"Dasen JS, De Camilli A, Wang B, Tucker PW, Jessell TM (2008) Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1. Cell 134:304\u2013316. https:\/\/doi.org\/10.1016\/j.cell.2008.06.019","journal-title":"Cell"},{"key":"2415_CR23","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.cell.2005.09.009","volume":"123","author":"JS Dasen","year":"2005","unstructured":"Dasen JS, Tice BC, Brenner-Morton S, Jessell TM (2005) A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity. Cell 123:477\u2013491. https:\/\/doi.org\/10.1016\/j.cell.2005.09.009","journal-title":"Cell"},{"key":"2415_CR24","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.cell.2011.09.037","volume":"147","author":"EY Demireva","year":"2011","unstructured":"Demireva EY, Shapiro LS, Jessell TM, Zampieri N (2011) Motor neuron position and topographic order imposed by beta- and gamma-catenin activities. Cell 147:641\u2013652. https:\/\/doi.org\/10.1016\/j.cell.2011.09.037","journal-title":"Cell"},{"key":"2415_CR25","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1093\/hmg\/ddae190","volume":"34","author":"JC Lee","year":"2025","unstructured":"Lee JC, Chung WK, Pisapia DJ, Henderson CE (2025) Motor pool selectivity of neuromuscular degeneration in type I spinal muscular atrophy is conserved between human and mouse. Hum Mol Genet 34:347\u2013367. https:\/\/doi.org\/10.1093\/hmg\/ddae190","journal-title":"Hum Mol Genet"},{"key":"2415_CR26","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.neuron.2010.12.032","volume":"69","author":"GZ Mentis","year":"2011","unstructured":"Mentis GZ, Blivis D, Liu W, Drobac E, Crowder ME, Kong L, Alvarez FJ, Sumner CJ, O\u2019Donovan MJ (2011) Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy. Neuron 69:453\u2013467. https:\/\/doi.org\/10.1016\/j.neuron.2010.12.032","journal-title":"Neuron"},{"key":"2415_CR27","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1007\/s00415-015-7721-8","volume":"262","author":"NG Simon","year":"2015","unstructured":"Simon NG, Lee M, Bae JS, Mioshi E, Lin CS, Pfluger CM, Henderson RD, Vucic S, Swash M, Burke D, Kiernan MC (2015) Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis. J Neurol 262:1424\u20131432. https:\/\/doi.org\/10.1007\/s00415-015-7721-8","journal-title":"J Neurol"},{"key":"2415_CR28","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1126\/science.8209258","volume":"264","author":"ME Gurney","year":"1994","unstructured":"Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX et al (1994) Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264:1772\u20131775. https:\/\/doi.org\/10.1126\/science.8209258","journal-title":"Science"},{"key":"2415_CR29","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1093\/hmg\/ddq021","volume":"19","author":"M Bowerman","year":"2010","unstructured":"Bowerman M, Beauvais A, Anderson CL, Kothary R (2010) Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model. Hum Mol Genet 19:1468\u20131478. https:\/\/doi.org\/10.1093\/hmg\/ddq021","journal-title":"Hum Mol Genet"},{"key":"2415_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.64","volume":"4","author":"J Guo","year":"2013","unstructured":"Guo J, Qiu W, Soh SL, Wei S, Radda GK, Ong WY, Pang ZP, Han W (2013) Motor neuron degeneration in a mouse model of seipinopathy. Cell Death Dis 4:e535. https:\/\/doi.org\/10.1038\/cddis.2013.64","journal-title":"Cell Death Dis"},{"key":"2415_CR31","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.cell.2021.12.014","volume":"185","author":"JI Chalif","year":"2022","unstructured":"Chalif JI, Martinez-Silva ML, Pagiazitis JG, Murray AJ, Mentis GZ (2022) Control of mammalian locomotion by ventral spinocerebellar tract neurons. Cell 185:328-344 e326. https:\/\/doi.org\/10.1016\/j.cell.2021.12.014","journal-title":"Cell"},{"key":"2415_CR32","doi-asserted-by":"publisher","first-page":"4069","DOI":"10.1523\/JNEUROSCI.16-13-04069.1996","volume":"16","author":"SG Carriedo","year":"1996","unstructured":"Carriedo SG, Yin HZ, Weiss JH (1996) Motor neurons are selectively vulnerable to AMPA\/kainate receptor-mediated injury in vitro. J Neurosci 16:4069\u20134079. https:\/\/doi.org\/10.1523\/JNEUROSCI.16-13-04069.1996","journal-title":"J Neurosci"},{"key":"2415_CR33","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/s0006-8993(00)01954-5","volume":"861","author":"YM Tsang","year":"2000","unstructured":"Tsang YM, Chiong F, Kuznetsov D, Kasarskis E, Geula C (2000) Motor neurons are rich in non-phosphorylated neurofilaments: cross-species comparison and alterations in ALS. Brain Res 861:45\u201358. https:\/\/doi.org\/10.1016\/s0006-8993(00)01954-5","journal-title":"Brain Res"},{"key":"2415_CR34","doi-asserted-by":"publisher","unstructured":"Biagioni F, Ferrucci M, Ryskalin L, Fulceri F, Lazzeri G, Calierno MT, Busceti CL, Ruffoli R, Fornai F. (2017). Protective effects of long-term lithium administration in a slowly progressive SMA mouse model. Arch Ital Biol. 155(4):118\u2013130. https:\/\/doi.org\/10.12871\/00039829201749.","DOI":"10.12871\/00039829201749"},{"key":"2415_CR35","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/0006-8993(86)91407-1","volume":"362","author":"LF Borges","year":"1986","unstructured":"Borges LF, Iversen SD (1986) Topography of choline acetyltransferase immunoreactive neurons and fibers in the rat spinal cord. Brain Res 362:140\u2013148. https:\/\/doi.org\/10.1016\/0006-8993(86)91407-1","journal-title":"Brain Res"},{"key":"2415_CR36","doi-asserted-by":"publisher","first-page":"5710","DOI":"10.1523\/JNEUROSCI.0274-05.2005","volume":"25","author":"JM Wilson","year":"2005","unstructured":"Wilson JM, Hartley R, Maxwell DJ, Todd AJ, Lieberam I, Kaltschmidt JA, Yoshida Y, Jessell TM, Brownstone RM (2005) Conditional rhythmicity of ventral spinal interneurons defined by expression of the Hb9 homeodomain protein. J Neurosci 25:5710\u20135719. https:\/\/doi.org\/10.1523\/JNEUROSCI.0274-05.2005","journal-title":"J Neurosci"},{"key":"2415_CR37","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/s0896-6273(01)80026-x","volume":"23","author":"S Arber","year":"1999","unstructured":"Arber S, Han B, Mendelsohn M, Smith M, Jessell TM, Sockanathan S (1999) Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron 23:659\u2013674. https:\/\/doi.org\/10.1016\/s0896-6273(01)80026-x","journal-title":"Neuron"},{"key":"2415_CR38","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awag045","author":"J Mecca","year":"2026","unstructured":"Mecca J, Mignot J, Gervais M, Ozturk T, Astord S, Berthier J, Bauche S, Messeant J, Biferi MG, Rouard H et al (2026) Targeted knockdown of Smn in muscle stem cells induces non-cell autonomous loss of motor neurons. Brain. https:\/\/doi.org\/10.1093\/brain\/awag045","journal-title":"Brain"},{"key":"2415_CR39","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.14670\/HH-11-983","volume":"33","author":"M Ferrucci","year":"2018","unstructured":"Ferrucci M, Lazzeri G, Flaibani M, Biagioni F, Cantini F, Madonna M, Bucci D, Limanaqi F, Soldani P, Fornai F (2018) In search for a gold standard procedure to count motor neurons in the spinal cord. Histol Histopathol 33:1021\u20131046. https:\/\/doi.org\/10.14670\/HH-11-983","journal-title":"Histol Histopathol"},{"key":"2415_CR40","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s00429-012-0501-7","volume":"219","author":"T Bacskai","year":"2014","unstructured":"Bacskai T, Rusznak Z, Paxinos G, Watson C (2014) Musculotopic organization of the motor neurons supplying the mouse hindlimb muscles: a quantitative study using Fluoro-Gold retrograde tracing. Brain Struct Funct 219:303\u2013321. https:\/\/doi.org\/10.1007\/s00429-012-0501-7","journal-title":"Brain Struct Funct"},{"key":"2415_CR41","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.jneumeth.2012.06.020","volume":"209","author":"BF El-Khodor","year":"2012","unstructured":"El-Khodor BF, Cirillo K, Beltran JA, Mushlin R, Winberg ML, Charney R, Chomicova O, Marino T, Ramboz S (2012) Prediction of death in the SMNDelta7 mouse model of spinal muscular atrophy: insight into disease stage and progression. J Neurosci Methods 209:259\u2013268. https:\/\/doi.org\/10.1016\/j.jneumeth.2012.06.020","journal-title":"J Neurosci Methods"},{"key":"2415_CR42","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1038\/nn.4561","volume":"20","author":"EV Fletcher","year":"2017","unstructured":"Fletcher EV, Simon CM, Pagiazitis JG, Chalif JI, Vukojicic A, Drobac E, Wang X, Mentis GZ (2017) Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy. Nat Neurosci 20:905\u2013916. https:\/\/doi.org\/10.1038\/nn.4561","journal-title":"Nat Neurosci"},{"key":"2415_CR43","doi-asserted-by":"publisher","first-page":"3767","DOI":"10.1016\/j.celrep.2017.12.003","volume":"21","author":"CM Simon","year":"2017","unstructured":"Simon CM, Dai Y, Van Alstyne M, Koutsioumpa C, Pagiazitis JG, Chalif JI, Wang X, Rabinowitz JE, Henderson CE, Pellizzoni L, Mentis GZ (2017) Converging mechanisms of p53 activation drive motor neuron degeneration in spinal muscular atrophy. Cell Rep 21:3767\u20133780. https:\/\/doi.org\/10.1016\/j.celrep.2017.12.003","journal-title":"Cell Rep"},{"key":"2415_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101236","volume":"3","author":"JM Buettner","year":"2022","unstructured":"Buettner JM, Kirmann T, Mentis GZ, Hallermann S, Simon CM (2022) Laser microscopy acquisition and analysis of premotor synapses in the murine spinal cord. STAR Protoc 3:101236. https:\/\/doi.org\/10.1016\/j.xpro.2022.101236","journal-title":"STAR Protoc"},{"key":"2415_CR45","doi-asserted-by":"publisher","first-page":"13588","DOI":"10.1073\/pnas.0906809106","volume":"106","author":"A Friese","year":"2009","unstructured":"Friese A, Kaltschmidt JA, Ladle DR, Sigrist M, Jessell TM, Arber S (2009) Gamma and alpha motor neurons distinguished by expression of transcription factor Err3. Proc Natl Acad Sci U S A 106:13588\u201313593. https:\/\/doi.org\/10.1073\/pnas.0906809106","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2415_CR46","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/1749-8104-4-42","volume":"4","author":"NA Shneider","year":"2009","unstructured":"Shneider NA, Brown MN, Smith CA, Pickel J, Alvarez FJ (2009) Gamma motor neurons express distinct genetic markers at birth and require muscle spindle-derived GDNF for postnatal survival. Neural Dev 4:42. https:\/\/doi.org\/10.1186\/1749-8104-4-42","journal-title":"Neural Dev"},{"key":"2415_CR47","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.cell.2016.01.027","volume":"165","author":"JB Bikoff","year":"2016","unstructured":"Bikoff JB, Gabitto MI, Rivard AF, Drobac E, Machado TA, Miri A, Brenner-Morton S, Famojure E, Diaz C, Alvarez FJ et al (2016) Spinal inhibitory interneuron diversity delineates variant motor microcircuits. Cell 165:207\u2013219. https:\/\/doi.org\/10.1016\/j.cell.2016.01.027","journal-title":"Cell"},{"key":"2415_CR48","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1002\/dvdy.24601","volume":"247","author":"TL Floyd","year":"2018","unstructured":"Floyd TL, Dai Y, Ladle DR (2018) Characterization of calbindin D28k expressing interneurons in the ventral horn of the mouse spinal cord. Dev Dyn 247:185\u2013193. https:\/\/doi.org\/10.1002\/dvdy.24601","journal-title":"Dev Dyn"},{"key":"2415_CR49","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1002\/ar.1090940210","volume":"94","author":"M Abercrombie","year":"1946","unstructured":"Abercrombie M (1946) Estimation of nuclear population from microtome sections. Anat Rec 94:239\u2013247. https:\/\/doi.org\/10.1002\/ar.1090940210","journal-title":"Anat Rec"},{"key":"2415_CR50","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1523\/JNEUROSCI.2142-20.2020","volume":"41","author":"CM Simon","year":"2021","unstructured":"Simon CM, Blanco-Redondo B, Buettner JM, Pagiazitis JG, Fletcher EV, Sime Longang JK, Mentis GZ (2021) Chronic pharmacological increase of neuronal activity improves sensory-motor dysfunction in spinal muscular atrophy mice. J Neurosci 41:376\u2013389. https:\/\/doi.org\/10.1523\/JNEUROSCI.2142-20.2020","journal-title":"J Neurosci"},{"key":"2415_CR51","doi-asserted-by":"publisher","first-page":"3885","DOI":"10.1016\/j.celrep.2019.11.058","volume":"29","author":"CM Simon","year":"2019","unstructured":"Simon CM, Van Alstyne M, Lotti F, Bianchetti E, Tisdale S, Watterson DM, Mentis GZ, Pellizzoni L (2019) Stasimon contributes to the loss of sensory synapses and motor neuron death in a mouse model of spinal muscular atrophy. Cell Rep 29:3885\u20133901. https:\/\/doi.org\/10.1016\/j.celrep.2019.11.058","journal-title":"Cell Rep"},{"key":"2415_CR52","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf336","author":"F Gerstner","year":"2025","unstructured":"Gerstner F, Wittig S, Menedo C, Ruwald S, Carlini MJ, Vankova A, Sowoidnich L, Martin-Lopez G, Dreilich V, Alonso Collado A et al (2025) Cerebellar pathology contributes to neurodevelopmental deficits in spinal muscular atrophy. Brain. https:\/\/doi.org\/10.1093\/brain\/awaf336","journal-title":"Brain"},{"key":"2415_CR53","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.1038276","volume":"16","author":"JM Buettner","year":"2022","unstructured":"Buettner JM, Sowoidnich L, Gerstner F, Blanco-Redondo B, Hallermann S, Simon CM (2022) p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models. Front Cell Neurosci 16:1038276. https:\/\/doi.org\/10.3389\/fncel.2022.1038276","journal-title":"Front Cell Neurosci"},{"key":"2415_CR54","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41592-020-01018-x","volume":"18","author":"C Stringer","year":"2021","unstructured":"Stringer C, Wang T, Michaelos M, Pachitariu M (2021) Cellpose: a generalist algorithm for cellular segmentation. Nat Methods 18:100\u2013106. https:\/\/doi.org\/10.1038\/s41592-020-01018-x","journal-title":"Nat Methods"},{"key":"2415_CR55","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1038\/s41592-022-01663-4","volume":"19","author":"M Pachitariu","year":"2022","unstructured":"Pachitariu M, Stringer C (2022) Cellpose 2.0: how to train your own model. Nat Methods 19:1634\u20131641. https:\/\/doi.org\/10.1038\/s41592-022-01663-4","journal-title":"Nat Methods"},{"key":"2415_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0086-4","volume":"8","author":"A Piras","year":"2017","unstructured":"Piras A, Schiaffino L, Boido M, Valsecchi V, Guglielmotto M, De Amicis E, Puyal J, Garcera A, Tamagno E, Soler RM, Vercelli A (2017) Inhibition of autophagy delays motoneuron degeneration and extends lifespan in a mouse model of spinal muscular atrophy. Cell Death Dis 8:3223. https:\/\/doi.org\/10.1038\/s41419-017-0086-4","journal-title":"Cell Death Dis"},{"key":"2415_CR57","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1007\/s13311-015-0399-x","volume":"13","author":"C Cervero","year":"2016","unstructured":"Cervero C, Montull N, Tarabal O, Piedrafita L, Esquerda JE, Caldero J (2016) Chronic treatment with the AMPK agonist AICAR prevents skeletal muscle pathology but fails to improve clinical outcome in a mouse model of severe spinal muscular atrophy. Neurotherapeutics 13:198\u2013216. https:\/\/doi.org\/10.1007\/s13311-015-0399-x","journal-title":"Neurotherapeutics"},{"key":"2415_CR58","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.88427","volume":"1","author":"MB Abera","year":"2016","unstructured":"Abera MB, Xiao J, Nofziger J, Titus S, Southall N, Zheng W, Moritz KE, Ferrer M, Cherry JJ, Androphy EJ et al (2016) ML372 blocks SMN ubiquitination and improves spinal muscular atrophy pathology in mice. JCI Insight 1:e88427. https:\/\/doi.org\/10.1172\/jci.insight.88427","journal-title":"JCI Insight"},{"key":"2415_CR59","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.nbd.2006.07.004","volume":"24","author":"LK Tsai","year":"2006","unstructured":"Tsai LK, Tsai MS, Lin TB, Hwu WL, Li H (2006) Establishing a standardized therapeutic testing protocol for spinal muscular atrophy. Neurobiol Dis 24:286\u2013295. https:\/\/doi.org\/10.1016\/j.nbd.2006.07.004","journal-title":"Neurobiol Dis"},{"key":"2415_CR60","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1101\/gad.316059.118","volume":"32","author":"M Van Alstyne","year":"2018","unstructured":"Van Alstyne M, Simon CM, Sardi SP, Shihabuddin LS, Mentis GZ, Pellizzoni L (2018) Dysregulation of Mdm2 and Mdm4 alternative splicing underlies motor neuron death in spinal muscular atrophy. Genes Dev 32:1045\u20131059. https:\/\/doi.org\/10.1101\/gad.316059.118","journal-title":"Genes Dev"},{"key":"2415_CR61","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.808479","volume":"13","author":"VM McLeod","year":"2022","unstructured":"McLeod VM, Chiam MDF, Perera ND, Lau CL, Boon WC, Turner BJ (2022) Mapping motor neuron vulnerability in the neuraxis of male SOD1(G93A) mice reveals widespread loss of androgen receptor occurring early in spinal motor neurons. Front Endocrinol (Lausanne) 13:808479. https:\/\/doi.org\/10.3389\/fendo.2022.808479","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2415_CR62","doi-asserted-by":"publisher","first-page":"E8316","DOI":"10.1073\/pnas.1605210113","volume":"113","author":"M Lalancette-Hebert","year":"2016","unstructured":"Lalancette-Hebert M, Sharma A, Lyashchenko AK, Shneider NA (2016) Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS. Proc Natl Acad Sci U S A 113:E8316\u2013E8325. https:\/\/doi.org\/10.1073\/pnas.1605210113","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2415_CR63","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.428","volume":"2","author":"A Austin","year":"2022","unstructured":"Austin A, Beresford L, Price G, Cunningham T, Kalmar B, Yon M (2022) Sectioning and counting of motor neurons in the L3 to L6 region of the adult mouse spinal cord. Curr Protoc 2:e428. https:\/\/doi.org\/10.1002\/cpz1.428","journal-title":"Curr Protoc"},{"key":"2415_CR64","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082654","volume":"8","author":"P d'Errico","year":"2013","unstructured":"d\u2019Errico P, Boido M, Piras A, Valsecchi V, De Amicis E, Locatelli D, Capra S, Vagni F, Vercelli A, Battaglia G (2013) Selective vulnerability of spinal and cortical motor neuron subpopulations in delta7 SMA mice. PLoS ONE 8:e82654. https:\/\/doi.org\/10.1371\/journal.pone.0082654","journal-title":"PLoS ONE"},{"key":"2415_CR65","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.neuroimage.2012.11.048","volume":"68","author":"M Harrison","year":"2013","unstructured":"Harrison M, O\u2019Brien A, Adams L, Cowin G, Ruitenberg MJ, Sengul G, Watson C (2013) Vertebral landmarks for the identification of spinal cord segments in the mouse. Neuroimage 68:22\u201329. https:\/\/doi.org\/10.1016\/j.neuroimage.2012.11.048","journal-title":"Neuroimage"},{"key":"2415_CR66","doi-asserted-by":"publisher","DOI":"10.3791\/55226","author":"M Richner","year":"2017","unstructured":"Richner M, Jager SB, Siupka P, Vaegter CB (2017) Hydraulic extrusion of the spinal cord and isolation of dorsal root ganglia in rodents. J Vis Exp. https:\/\/doi.org\/10.3791\/55226","journal-title":"J Vis Exp"},{"key":"2415_CR67","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.neuron.2015.05.045","volume":"87","author":"AI Mendelsohn","year":"2015","unstructured":"Mendelsohn AI, Simon CM, Abbott LF, Mentis GZ, Jessell TM (2015) Activity regulates the incidence of heteronymous sensory-motor connections. Neuron 87:111\u2013123. https:\/\/doi.org\/10.1016\/j.neuron.2015.05.045","journal-title":"Neuron"},{"key":"2415_CR68","doi-asserted-by":"publisher","first-page":"3201","DOI":"10.1038\/s41598-019-39881-0","volume":"9","author":"D Blivis","year":"2019","unstructured":"Blivis D, Falgairolle M, O\u2019Donovan MJ (2019) Dye-coupling between neonatal spinal motoneurons and interneurons revealed by prolonged back-filling of a ventral root with a low molecular weight tracer in the mouse. Sci Rep 9:3201. https:\/\/doi.org\/10.1038\/s41598-019-39881-0","journal-title":"Sci Rep"},{"key":"2415_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-95143-y","volume":"11","author":"LM Koronfel","year":"2021","unstructured":"Koronfel LM, Kanning KC, Alcos A, Henderson CE, Brownstone RM (2021) Elimination of glutamatergic transmission from Hb9 interneurons does not impact treadmill locomotion. Sci Rep 11:16008. https:\/\/doi.org\/10.1038\/s41598-021-95143-y","journal-title":"Sci Rep"},{"key":"2415_CR71","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/B978-0-444-53613-6.00006-X","volume":"187","author":"RM Brownstone","year":"2010","unstructured":"Brownstone RM, Bui TV (2010) Spinal interneurons providing input to the final common path during locomotion. Prog Brain Res 187:81\u201395. https:\/\/doi.org\/10.1016\/B978-0-444-53613-6.00006-X","journal-title":"Prog Brain Res"},{"key":"2415_CR72","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1111\/joa.12419","volume":"228","author":"RA Powis","year":"2016","unstructured":"Powis RA, Gillingwater TH (2016) Selective loss of alpha motor neurons with sparing of gamma motor neurons and spinal cord cholinergic neurons in a mouse model of spinal muscular atrophy. J Anat 228:443\u2013451. https:\/\/doi.org\/10.1111\/joa.12419","journal-title":"J Anat"},{"key":"2415_CR73","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1002\/ar.23728","volume":"301","author":"J Bahney","year":"2018","unstructured":"Bahney J, von Bartheld CS (2018) The cellular composition and glia-neuron ratio in the spinal cord of a human and a nonhuman primate: comparison with other species and brain regions. Anat Rec 301:697\u2013710. https:\/\/doi.org\/10.1002\/ar.23728","journal-title":"Anat Rec"},{"key":"2415_CR74","doi-asserted-by":"publisher","DOI":"10.1111\/nan.13013","volume":"50","author":"H Allardyce","year":"2024","unstructured":"Allardyce H, Lawrence BD, Crawford TO, Sumner CJ, Parson SH (2024) A reassessment of spinal cord pathology in severe infantile spinal muscular atrophy: reassessment of spinal cord pathology. Neuropathol Appl Neurobiol 50:e13013. https:\/\/doi.org\/10.1111\/nan.13013","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2415_CR75","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/s0387-7604(82)80002-8","volume":"4","author":"T Kumagai","year":"1982","unstructured":"Kumagai T, Hashizume Y (1982) Morphological and morphometric studies on the spinal cord lesion in Werdnig-Hoffmann disease. Brain Dev 4:87\u201396. https:\/\/doi.org\/10.1016\/s0387-7604(82)80002-8","journal-title":"Brain Dev"},{"key":"2415_CR76","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf074","author":"CM Simon","year":"2025","unstructured":"Simon CM, Delestree N, Montes J, Sowoidnich L, Gerstner F, Carranza E, Buettner JM, Pagiazitis JG, Prat-Ortega G, Ensel S et al (2025) Proprioceptive synaptic dysfunction is a key feature in mice and humans with spinal muscular atrophy. Brain. https:\/\/doi.org\/10.1093\/brain\/awaf074","journal-title":"Brain"},{"key":"2415_CR77","doi-asserted-by":"publisher","unstructured":"Kong L, Valdivia DO, Simon CM, Hassinan CW, Delestree N, Ramos DM, Park JH, Pilato, C.M., Xu, X., Crowder, M., et al. (2021). Impaired prenatal motor axon development necessitates early therapeutic intervention in severe SMA. Sci Transl Med, 13. https:\/\/doi.org\/10.1126\/scitranslmed.abb6871.","DOI":"10.1126\/scitranslmed.abb6871"},{"key":"2415_CR78","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-38","volume":"11","author":"HC Liu","year":"2013","unstructured":"Liu HC, Ting CH, Wen HL, Tsai LK, Hsieh-Li HM, Li H, Lin-Chao S (2013) Sodium vanadate combined with L-ascorbic acid delays disease progression, enhances motor performance, and ameliorates muscle atrophy and weakness in mice with spinal muscular atrophy. BMC Med 11:38. https:\/\/doi.org\/10.1186\/1741-7015-11-38","journal-title":"BMC Med"},{"key":"2415_CR79","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13081821","author":"S Neuhoff","year":"2025","unstructured":"Neuhoff S, Schmitt LI, Liebig KC, Hezel S, Tilahun NI, Kleinschnitz C, Leo M, Hagenacker T (2025) Neuronal Pentraxin 2 as a potential biomarker for nusinersen therapy response in adults with spinal muscular atrophy: a pilot study. Biomedicines. https:\/\/doi.org\/10.3390\/biomedicines13081821","journal-title":"Biomedicines"},{"key":"2415_CR80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0267990","volume":"17","author":"MJ Carlini","year":"2022","unstructured":"Carlini MJ, Triplett MK, Pellizzoni L (2022) Neuromuscular denervation and deafferentation but not motor neuron death are disease features in the Smn2B\/- mouse model of SMA. PLoS ONE 17:e0267990. https:\/\/doi.org\/10.1371\/journal.pone.0267990","journal-title":"PLoS ONE"},{"key":"2415_CR81","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1177\/0145445516673998","volume":"41","author":"D Drevon","year":"2017","unstructured":"Drevon D, Fursa SR, Malcolm AL (2017) Intercoder reliability and validity of WebPlotDigitizer in extracting graphed data. Behav Modif 41:323\u2013339. https:\/\/doi.org\/10.1177\/0145445516673998","journal-title":"Behav Modif"},{"key":"2415_CR82","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JP Higgins","year":"2003","unstructured":"Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557\u2013560. https:\/\/doi.org\/10.1136\/bmj.327.7414.557","journal-title":"BMJ"},{"key":"2415_CR83","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1093\/hmg\/dds540","volume":"22","author":"B Ackermann","year":"2013","unstructured":"Ackermann B, Krober S, Torres-Benito L, Borgmann A, Peters M, Hosseini Barkooie SM, Tejero R, Jakubik M, Schreml J, Milbradt J et al (2013) Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality. Hum Mol Genet 22:1328\u20131347. https:\/\/doi.org\/10.1093\/hmg\/dds540","journal-title":"Hum Mol Genet"},{"key":"2415_CR84","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1093\/hmg\/ddp562","volume":"19","author":"CM Simon","year":"2010","unstructured":"Simon CM, Jablonka S, Ruiz R, Tabares L, Sendtner M (2010) Ciliary neurotrophic factor-induced sprouting preserves motor function in a mouse model of mild spinal muscular atrophy. Hum Mol Genet 19:973\u2013986. https:\/\/doi.org\/10.1093\/hmg\/ddp562","journal-title":"Hum Mol Genet"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-026-02415-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-026-02415-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-026-02415-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:17:38Z","timestamp":1788279458000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40478-026-02415-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":83,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2415"],"URL":"https:\/\/doi.org\/10.1186\/s40478-026-02415-7","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"23 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All procedures involving human and animal material were conducted in accordance with relevant institutional and national ethical guidelines. Human postmortem tissues were obtained at autopsy at Johns Hopkins University (Baltimore, MD, USA) following informed consent from parents or patients\u2019 legal representatives and in strict compliance with applicable legal and institutional regulations. All animal experiments were conducted in compliance with institutional and national guidelines for the care and use of laboratory animals. Procedures performed at Leipzig University (Leipzig, Saxony, Germany) adhered to European legislation (Council Directive 86\/609\/EEC) and the German Animal Welfare Act (Tierschutzgesetz), and were approved by the competent regional authority (Landesdirektion Leipzig, Saxony). Experiments carried out at Columbia University (New York, NY, USA) were conducted in accordance with the guidelines of the National Institutes of Health for the Care and Use of Laboratory Animals and were approved by the Columbia University Institutional Animal Care and Use Committee (IACUC).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors report no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"182"}}