{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:20:52Z","timestamp":1792066852187,"version":"4.4.0"},"reference-count":75,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2019\u20102679"],"award-info":[{"award-number":["PICT 2019\u20102679"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PIP 2023\u20102025"],"award-info":[{"award-number":["PIP 2023\u20102025"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Neuronal polarization is a fundamental process in the formation of functional neural circuits, relying on the precise coordination between cytoskeletal regulatory signals and mechanisms that sustain cellular integrity. Disruption of these processes compromises neuronal differentiation and survival, and various neurotoxic compounds, including certain pesticides, have been associated with such dysfunctions. In this context, identifying molecules that counteract these detrimental effects is of significant therapeutic interest. Neuronal polarization is essential for the establishment of functional neural circuits and relies on coordinated regulation of actin cytoskeleton dynamics, RhoA\/ROCK signaling, and mitochondrial function. Here, we investigated the neuroprotective and neurorestorative potential of the ganglioside GM1 and its oligosaccharide derivative, osGM1, in primary hippocampal pyramidal neurons derived from embryonic day 18 (E18) rat embryos exposed to the mitochondrial neurotoxin rotenone. Rotenone induced a marked arrest of neuronal development, impaired axonal elongation, and disrupted mitochondrial organization and functional status. Both GM1 and osGM1 promoted recovery of neuronal polarity and axonal growth, exerting protective and restorative effects even under continuous toxin exposure, with osGM1 showing superior efficacy. Notably, osGM1 also reversed axonal growth deficits caused by pathological actin stabilization. Mechanistically, osGM1 normalized rotenone\u2010induced hyperactivation of the RhoA\/ROCK pathway without altering basal signaling and partially restored mitochondrial network integrity and functional activity. Collectively, these findings identify osGM1 as a multi\u2010target modulator of cytoskeletal and mitochondrial dysfunction and support its translational potential as a therapeutic strategy to counteract neurotoxin\u2010induced neuronal damage.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70505-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70505","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:20:44Z","timestamp":1782904844000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>\n                      GM\n                      <sub>1<\/sub>\n                    <\/scp>\n                    \u2010Oligosaccharide Rescues Rotenone\u2010Impaired Neuronal Polarization Through\n                    <scp>RhoA<\/scp>\n                    \/\n                    <scp>ROCK<\/scp>\n                    Modulation and Mitochondrial Protection"],"prefix":"10.1111","volume":"170","author":[{"given":"Pablo E. A.","family":"Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Secretar\u00eda de Ciencia y Tecnolog\u00eda, Ministerio de Producci\u00f3n, Ciencia e Innovaci\u00f3n Tecnol\u00f3gica Gobierno de la Provincia de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo N.","family":"Colmano","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Biol\u00f3gica Ranwel Caputto, Facultad de Ciencias Qu\u00edmicas Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra (INIMEC), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-5474","authenticated-orcid":false,"given":"Mar\u00eda E.","family":"Mariani","sequence":"additional","affiliation":[{"name":"CeTBIO, Centro de Transferencia de Bioinsumos, Facultad de Ciencias Agropecuarias Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"},{"name":"Ciudad Universitaria Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana B.","family":"Rosso","sequence":"additional","affiliation":[{"name":"Laboratorio de Toxicolog\u00eda Experimental, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario, Argentina (CONICET)  Rosario, Santa Fe Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Quassollo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra (INIMEC), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-8685","authenticated-orcid":false,"given":"Pablo","family":"Helguera","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra (INIMEC), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Bisbal","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra (INIMEC), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba 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