{"id":20389,"date":"2018-04-04T17:28:59","date_gmt":"2018-04-04T15:28:59","guid":{"rendered":"https:\/\/neurodev-ng.u-bordeaux.fr\/matthieu-bastide-erwan-bezard-et-al-in-neurobiol-dis\/"},"modified":"2018-04-04T17:28:59","modified_gmt":"2018-04-04T15:28:59","slug":"matthieu-bastide-erwan-bezard-et-al-in-neurobiol-dis","status":"publish","type":"post","link":"https:\/\/www.bordeaux-neurocampus.fr\/en\/matthieu-bastide-erwan-bezard-et-al-in-neurobiol-dis\/","title":{"rendered":"Matthieu Bastide, Erwan B\u00e9zard et al. in <em>Neurobiol Dis.<\/em>"},"content":{"rendered":"<p><em><strong><a class=\"external\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26480869\">Striatal NELF-mediated RNA polymerase II stalling controls l-dopa induced dyskinesia<\/a>.<\/strong>\u00a0<\/em><em>Bastide MF, Bido S, Duteil N, B\u00e9zard E.<br \/>\nNeurobiol Dis. 2015 Oct 19;85:93-98. doi: 10.1016\/j.nbd.2015.10.013.<\/em><\/p>\n<p><strong><br \/>\n<\/strong><strong><a class=\"pirobox\" title=\"\" href=\"https:\/\/www.bordeaux-neurocampus.fr\/_contents\/ametys-internal%253Asites\/neurosciences\/ametys-internal%253Acontents\/bastide-neurobiol-dis-actualite\/_metadata\/content\/_data\/Bastide-M160-2.jpg\"  rel=\"lightbox[20389] single\"><img loading=\"lazy\" decoding=\"async\" class=\"alignleft\" src=\"https:\/\/www.bordeaux-neurocampus.fr\/_contents-images\/ametys-internal%253Asites\/neurosciences\/ametys-internal%253Acontents\/bastide-neurobiol-dis-actualite\/_metadata\/content\/_data\/Bastide-M160-2.jpg_172x120\" alt=\"\" width=\"120\" height=\"172\" \/><\/a> <\/strong><strong>Involvement of transcriptional mechanisms in L-DOPA induced dyskinesia<\/strong><\/p>\n<p>Chronic treatment of Parkinson\u2019s disease (PD) patients with the dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) induces the development of involuntary movements, known as L-DOPA-induced dyskinesia (LID). LID result in a rapid striatal overexpression of several molecular markers, in particular the members of the immediate-early gene (IEG) family, a class of genes rapidly transcribed in response to an external stimulus, including \u0394FosB, ARC and Zif268. Down-regulating the expression of \u2206FosB or inactivating \u2206FosB-expressing neurons, decrease LID severity both in rodents and non-human primates. These data highlight the key role of IEG in LID manifestation. However, the transcriptional-related mechanisms inducing a rapid IEG expression in LID remain unclear. Recent evidences suggest that expression of many IEG depends on a prior recruitment of the RNA polymerase II, which initiates transcription elongation and stalls after transcribing a short piece of mRNA near the promoter. RNA polymerase II stalling is critically regulated by a protein complex, the negative elongation factor (NELF), composed of four essential subunits: NELF-A, -B, -C\/D and \u2013E. NELF-mediated RNA polymerase II stalling on IEG promoters poises them for rapid transcription within few minutes after an external stimulus . While the in vitro machinery is well described, the role of NELF-mediated RNA polymerase II stalling remains however to be demonstrated in vivo in physiological and pathological states.<\/p>\n<p><strong>Therefore, to assess the precise role of NELF-<\/strong>mediated RNA polymerase II stalling upon LID severity, we decrease the levels of the NELF essential subunit NELF-E using a lentiviral vector (LV) delivering a short spin RNA (shRNA) against NELF-E mRNA in the striatum of dyskinetic 6-hydroxydopamine (6-OHDA) lesioned rats. The depletion of NELF-E reduced the severity of LID manifestation without affecting the beneficial effect of L-Dopa associated with a decrease in \u0394FosB, ARC and Zif268 expression.<\/p>\n<p class=\"content-contact\">Contact \/ Erwan B\u00e9zard \/ Directeur de l&#8217;IMN<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Involvement of transcriptional mechanisms in L-DOPA induced dyskinesia<\/p>\n","protected":false},"author":108,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[71],"tags":[],"class_list":["post-20389","post","type-post","status-publish","format-standard","hentry","category-highlight-en"],"_links":{"self":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/20389","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/users\/108"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/comments?post=20389"}],"version-history":[{"count":0,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/20389\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media?parent=20389"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/categories?post=20389"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/tags?post=20389"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}