{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:16:51Z","timestamp":1789791411119,"version":"4.0.1"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T00:00:00Z","timestamp":1715472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ipsen"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum neurotoxins E (BoNT\/E) and A (BoNT\/A) act by cleaving Synaptosome-Associated Protein 25 (SNAP25) at two different C-terminal sites, but they display very distinct durations of action, BoNT\/E being short acting and BoNT\/A long acting. We investigated the duration of action, spread and neuronal transport of BoNT\/E (6.5 ng\/kg) and BoNT\/A (125 pg\/kg) after single intramuscular administrations of high equivalent efficacious doses, in rats, over a 30- or 75-day periods, respectively. To achieve this, we used (i) digit abduction score assay, (ii) immunohistochemistry for SNAP25 (N-ter part; SNAP25N-ter and C-ter part; SNAP25C-ter) and its cleavage sites (cleaved SNAP25; c-SNAP25E and c-SNAP25A) and (iii) muscular changes in histopathology evaluation. Combined in vivo observation and immunohistochemistry analysis revealed that, compared to BoNT\/A, BoNT\/E induces minimal muscular changes, possesses a lower duration of action, a reduced ability to spread and a decreased capacity to be transported to the lumbar spinal cord. Interestingly, SNAP25C-ter completely disappeared for both toxins during the peak of efficacy, suggesting that the persistence of toxin effects is driven by the persistence of proteases in tissues. These data unveil some new molecular mechanisms of action of the short-acting BoNT\/E and long-acting BoNT\/A, and reinforce their overall safety profiles.<\/jats:p>","DOI":"10.3390\/toxins16050225","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T09:28:25Z","timestamp":1715592505000},"page":"225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Intramuscular Botulinum Neurotoxin Serotypes E and A Elicit Distinct Effects on SNAP25 Protein Fragments, Muscular Histology, Spread and Neuronal Transport: An Integrated Histology-Based Study in the Rat"],"prefix":"10.3390","volume":"16","author":[{"given":"Vincent","family":"Martin","sequence":"first","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3222-2137","authenticated-orcid":false,"given":"Denis","family":"Carre","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heloise","family":"Bilbault","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5079-4212","authenticated-orcid":false,"given":"Sebastien","family":"Oster","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Limana","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Sebal","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Favre-Guilmard","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6621-6339","authenticated-orcid":false,"given":"Mikhail","family":"Kalinichev","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Leveque","sequence":"additional","affiliation":[{"name":"Aix-Marseille University, INSERM, DyNaMo U1325, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Boulifard","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"George","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Lezmi","sequence":"additional","affiliation":[{"name":"Ipsen Innovation, 91940 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nrmicro3295","article-title":"Botulinum Neurotoxins: Genetic, Structural and Mechanistic Insights","volume":"12","author":"Rossetto","year":"2014","journal-title":"Nat. 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