ALDH1A1 regulates postsynaptic μ–opioid receptor expression in dorsal striatal projection neurons and mitigates dyskinesia through transsynaptic retinoic acid signaling
Date
2019Journal
Scientific ReportsPublisher
Springer NatureType
Article
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Aldehyde 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.Sponsors
This 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).Rights/Terms
Open 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.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062586730&doi=10.1038%2fs41598-019-40326-x&partnerID=40&md5=da7c19357a0e9891a65b98562fdc08de; http://hdl.handle.net/10713/8867ae974a485f413a2113503eed53cd6c53
10.1038/s41598-019-40326-x