{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:08:32Z","timestamp":1790885312012,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KO 1674\/5-1"],"award-info":[{"award-number":["KO 1674\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The brain-derived neurotrophic factor (BDNF) plays crucial roles in both the developing and mature brain. Moreover, alterations in BDNF levels are correlated with the cognitive impairment observed in several neurological diseases. Among the different therapeutic strategies developed to improve endogenous BDNF levels is the administration of the BDNF-inducing drug Fingolimod, an agonist of the sphingosine-1-phosphate receptor. Fingolimod treatment was shown to rescue diverse symptoms associated with several neurological conditions (i.e., Alzheimer disease, Rett syndrome). However, the cellular mechanisms through which Fingolimod mediates its BDNF-dependent therapeutic effects remain unclear. We show that Fingolimod regulates the dendritic architecture, dendritic spine density and morphology of healthy mature primary hippocampal neurons. Moreover, the application of Fingolimod upregulates the expression of activity-related proteins c-Fos and pERK1\/2 in these cells. Importantly, we show that BDNF release is required for these actions of Fingolimod. As alterations in neuronal structure underlie cognitive impairment, we tested whether Fingolimod application might prevent the abnormalities in neuronal structure typical of two neurodevelopmental disorders, namely Rett syndrome and Cdk5 deficiency disorder. We found a significant rescue in the neurite architecture of developing cortical neurons from Mecp2 and Cdkl5 mutant mice. Our study provides insights into understanding the BDNF-dependent therapeutic actions of Fingolimod.<\/jats:p>","DOI":"10.3390\/ijms21093079","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T05:05:32Z","timestamp":1588050332000},"page":"3079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Fingolimod Modulates Dendritic Architecture in a BDNF-Dependent Manner"],"prefix":"10.3390","volume":"21","author":[{"given":"Abhisarika","family":"Patnaik","sequence":"first","affiliation":[{"name":"Zoological Institute, Division of Cellular Neurobiology, TU Braunschweig, D-38106 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9221-4908","authenticated-orcid":false,"given":"Eleonora","family":"Spiombi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0963-9789","authenticated-orcid":false,"given":"Angelisa","family":"Frasca","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Landsberger","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zagrebelsky","sequence":"additional","affiliation":[{"name":"Zoological Institute, Division of Cellular Neurobiology, TU Braunschweig, D-38106 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6956-5913","authenticated-orcid":false,"given":"Martin","family":"Korte","sequence":"additional","affiliation":[{"name":"Zoological Institute, Division of Cellular Neurobiology, TU Braunschweig, D-38106 Braunschweig, Germany"},{"name":"Helmholtz Centre for Infection Research, AG NIND, Inhoffenstr. 7, D-38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/j.1460-2075.1982.tb01207.x","article-title":"Purification of a new neurotrophic factor from mammalian brain","volume":"1","author":"Barde","year":"1982","journal-title":"EMBO J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/dneu.20774","article-title":"Brain-derived neurotrophic factor and the development of structural neuronal connectivity","volume":"70","author":"Kidane","year":"2010","journal-title":"Dev. 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