{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:48:00Z","timestamp":1792140480463,"version":"4.4.0"},"reference-count":111,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SI 1969\/7-1"],"award-info":[{"award-number":["SI 1969\/7-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01NS102451"],"award-info":[{"award-number":["R01NS102451"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01NS114218"],"award-info":[{"award-number":["R01NS114218"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01NS116400"],"award-info":[{"award-number":["R01NS116400"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01NS078375"],"award-info":[{"award-number":["R01NS078375"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01NS125362"],"award-info":[{"award-number":["R01NS125362"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by ubiquitous survival motor neuron (SMN) deficiency and loss of motor neurons. The persistence of motor and communication impairments, together with emerging cognitive and social deficits in severe type I SMA patients treated early with SMN-restoring therapies, suggests a broader dysfunction involving neural circuits of the brain.<\/jats:p>\n                  <jats:p>To explore the potential supraspinal contributions to these emerging phenotypes, we investigated the cerebellum, a brain region crucial for both motor and cognitive behaviours. Here, we identify cerebellar pathology in both post-mortem tissue from type I SMA patients and a severe mouse model, which is characterized by lobule-specific Purkinje cell death driven by cell-autonomous, non-apoptotic p53-dependent mechanisms. Loss and dysfunction of excitatory parallel fibre synapses onto Purkinje cells contribute further to cerebellar circuit disruption and altered Purkinje cell firing. Furthermore, we identified impaired ultrasonic vocalization (a proxy for early-developing social communication skills that depend on cerebellar function) in a severe SMA mouse model. Cell-specific rescue experiments demonstrate that intrinsic cerebellar pathology contributes to motor and social communication impairments independently of spinal motor circuit abnormalities.<\/jats:p>\n                  <jats:p>Together, these findings establish cerebellar dysfunction as a pathogenic driver of neurodevelopmental motor and social defects, providing mechanistic insight into the persisting and emerging phenotypes of SMA.<\/jats:p>","DOI":"10.1093\/brain\/awaf336","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T12:06:46Z","timestamp":1757678806000},"page":"840-855","source":"Crossref","is-referenced-by-count":9,"title":["Cerebellar pathology contributes to neurodevelopmental deficits in spinal muscular atrophy"],"prefix":"10.1093","volume":"149","author":[{"given":"Florian","family":"Gerstner","sequence":"first","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Wittig","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Menedo","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayan","family":"Ruwald","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J","family":"Carlini","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Vankova","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Sowoidnich","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Mart\u00edn-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Dreilich","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Alonso-Collado","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G","family":"Pagiazitis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oumayma","family":"Aousji","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Biomedical Research (ZBF), Ulm University , Ulm, Baden-W\u00fcrttemberg 89081 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Grzyb","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy K","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["USA"]},{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["USA"]},{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine , Baltimore, MD 21218 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu","family":"Yang","sequence":"additional","affiliation":[{"name":"Mouse Neurobehavioral Core Facility, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9935-6899","authenticated-orcid":false,"given":"Francesco","family":"Roselli","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Biomedical Research (ZBF), Ulm University , Ulm, Baden-W\u00fcrttemberg 89081 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) , Ulm, Baden-W\u00fcrttemberg 89081 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Z","family":"Mentis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Pathology and Cell Biology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte J","family":"Sumner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["USA"]},{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["USA"]},{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine , Baltimore, MD 21218 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livio","family":"Pellizzoni","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Pathology and Cell Biology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M","family":"Simon","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"2026030512070665800_awaf336-B1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.cell.2021.10.029","article-title":"Central nervous system regeneration","volume":"185","author":"Varadarajan","year":"2022","journal-title":"Cell"},{"key":"2026030512070665800_awaf336-B2","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1152\/jn.00833.2018","article-title":"Synapse formation: From cellular and molecular mechanisms to neurodevelopmental and neurodegenerative disorders","volume":"121","author":"Batool","year":"2019","journal-title":"J 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