{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T16:55:27Z","timestamp":1775235327790,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","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":[[2018,12]]},"abstract":"Abstract<\/jats:title>Parkinson's disease (PD<\/jats:styled-content>) is characterized by the loss of midbrain dopaminergic neurons and aggregates of \u03b1\u2010synuclein termed Lewy bodies. Fingolimod (FTY<\/jats:styled-content>720) is an agonist of sphingosine\u20101 phosphate receptors and an approved oral treatment for multiple sclerosis. Fingolimod elevates brain\u2010derived neurotrophic factor (BDNF<\/jats:styled-content>), an important neurotrophic factor for dopaminergic neurons. BDNF<\/jats:styled-content> and fingolimod are beneficial in several animal models of PD<\/jats:styled-content>. In order to validate the therapeutic potential of fingolimod for the treatment of PD<\/jats:styled-content>, we tested its effect in the subacute MPTP<\/jats:styled-content> mouse model of PD<\/jats:styled-content>. MPTP<\/jats:styled-content> or vehicle was applied i.p. in doses of 30\u00a0mg\/kg MPTP<\/jats:styled-content> on five consecutive days. In order to recapitulate the combination of dopamine loss and \u03b1\u2010synuclein aggregates found in PD<\/jats:styled-content>, MPTP<\/jats:styled-content> was first administered in Thy1\u2010A30P\u2010\u03b1\u2010synuclein transgenic mice. Fingolimod was administered i.p. at a dose of 0.1\u00a0mg\/kg every second day. Nigrostriatal degeneration was assayed by stereologically counting the number of dopaminergic neurons in the substantia nigra pars compacta, by analysing the concentration of catecholamines and the density of dopaminergic fibres in the striatum. MPTP<\/jats:styled-content> administration produced a robust nigrostriatal degeneration, comparable to previous studies. Unexpectedly, we found no difference between mice with and without fingolimod treatment, neither at baseline, nor at 14 or 90\u00a0days after MPTP<\/jats:styled-content>. Also, we found no effect of fingolimod in the subacute MPTP<\/jats:styled-content> mouse model when we used wildtype mice instead of \u03b1\u2010synuclein transgenic mice, and no effect with an increased dose of 1\u00a0mg\/kg fingolimod administered every day. In order to explain these findings, we analysed BDNF<\/jats:styled-content> regulation by fingolimod. We did find an increase of BDNF<\/jats:styled-content> protein after a single injection of fingolimod 0.1 or 1.0\u00a0mg\/kg, but not after multiple injections, indicating that the BDNF<\/jats:styled-content> response to fingolimod is unsustainable over time. Taken together we did not observe a neuroprotective effect of fingolimod in the subacute MPTP<\/jats:styled-content> mouse model of PD<\/jats:styled-content>. We discuss possible explanations for this discrepancy with previous findings and conclude fingolimod might be beneficial for the nonmotor symptoms of PD<\/jats:styled-content>.<\/jats:p><\/jats:sec>Open Science Badges<\/jats:title><\/jats:p><\/jats:p>This article has received a badge for *Open Materials<\/jats:bold>* and *Open Data<\/jats:bold>* because it provided all relevant information to reproduce the study in the manuscript and because it made the data publicly available. The data can be accessed at https:\/\/osf.io\/6xgfn\/<\/jats:ext-link>. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link>.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14575","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T04:09:44Z","timestamp":1535602184000},"page":"678-691","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Fingolimod (FTY720) is not protective in the subacute MPTP mouse model of Parkinson's disease and does not lead to a sustainable increase of brain\u2010derived neurotrophic factor"],"prefix":"10.1111","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6312-5236","authenticated-orcid":false,"given":"Daniel","family":"Komnig","sequence":"first","affiliation":[{"name":"Department of Neurology RWTH Aachen University Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toruntay Cem","family":"Dagli","sequence":"additional","affiliation":[{"name":"Department of Neurology RWTH Aachen University Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pardes","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Neurology RWTH Aachen University Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Zeyen","sequence":"additional","affiliation":[{"name":"Department of Neurology RWTH Aachen University Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8903-0593","authenticated-orcid":false,"given":"J\u00f6rg B.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Neurology RWTH Aachen University Aachen Germany"},{"name":"JARA\u2010BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum J\u00fclich GmbH and RWTH Aachen University Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-526X","authenticated-orcid":false,"given":"Bj\u00f6rn H.","family":"Falkenburger","sequence":"additional","affiliation":[{"name":"Department of Neurology RWTH Aachen University Aachen Germany"},{"name":"JARA\u2010BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum J\u00fclich GmbH and RWTH Aachen University Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2010.12.018"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(01)00003-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70049-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-0618(01)00115-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014154108"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24217"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206093109"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt615"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.249"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.263"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-24-09126.2000"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13618"},{"key":"e_1_2_7_15_1","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Franklin K. 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