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dc.contributor.authorPan, j.
dc.contributor.authorYu, J.
dc.contributor.authorSun, L.
dc.date.accessioned2019-04-25T17:28:23Z
dc.date.available2019-04-25T17:28:23Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85062586730&doi=10.1038%2fs41598-019-40326-x&partnerID=40&md5=da7c19357a0e9891a65b98562fdc08de
dc.identifier.urihttp://hdl.handle.net/10713/8867
dc.description.abstractAldehyde dehydrogenase 1A1 (ALDH1A1), a retinoic acid (RA) synthase, is selectively expressed by the nigrostriatal dopaminergic (nDA) neurons that preferentially degenerate in Parkinson’s disease (PD). ALDH1A1–positive axons mainly project to the dorsal striatum. However, whether ALDH1A1 and its products regulate the activity of postsynaptic striatal neurons is unclear. Here we show that μ–type opioid receptor (MOR1) levels were severely decreased in the dorsal striatum of postnatal and adult Aldh1a1 knockout mice, whereas dietary supplement of RA restores its expression. Furthermore, RA treatment also upregulates striatal MOR1 levels and signaling and alleviates L-DOPA–induced dyskinetic movements in pituitary homeobox 3 (Pitx3)–defcient mice that lack of ALDH1A1–expressing nDA neurons. Therefore, our fndings demonstrate that ALDH1A1–synthesized RA is required for postsynaptic MOR1 expression in the postnatal and adult dorsal striatum, supporting potential therapeutic benefts of RA supplementation in moderating L-DOPA–induced dyskinesia.en_US
dc.description.sponsorshipThis work was supported in part by the intramural research programs of National Institute on Aging, National Institutes of Health (HC: AG000928) and National Natural Science Foundation of China (WL: 81430021, JP: 81371409).en_US
dc.description.urihttps://doi.org/10.1038/s41598-019-40326-xen_US
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofScientific Reportsen_US
dc.rightsOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.subjectaldehyde dehydrogenase 1A1en_US
dc.subject.meshDyskinesia, Drug-Induceden_US
dc.subject.meshLevodopaen_US
dc.titleALDH1A1 regulates postsynaptic μ–opioid receptor expression in dorsal striatal projection neurons and mitigates dyskinesia through transsynaptic retinoic acid signalingen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-019-40326-xen_us
dc.identifier.ispublishedNoen_US
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