ALDH1A1 regulates postsynaptic μ–opioid receptor expression in dorsal striatal projection neurons and mitigates dyskinesia through transsynaptic retinoic acid signaling View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Jing Pan, Jia Yu, Lixin Sun, Chengsong Xie, Lisa Chang, Junbing Wu, Sarah Hawes, Sara Saez–Atienzar, Wang Zheng, Justin Kung, Jinhui Ding, Weidong Le, Shengdi Chen, Huaibin Cai

ABSTRACT

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)-deficient mice that lack of ALDH1A1-expressing nDA neurons. Therefore, our findings demonstrate that ALDH1A1-synthesized RA is required for postsynaptic MOR1 expression in the postnatal and adult dorsal striatum, supporting potential therapeutic benefits of RA supplementation in moderating L-DOPA-induced dyskinesia. More... »

PAGES

3602

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-40326-x

DOI

http://dx.doi.org/10.1038/s41598-019-40326-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112544111

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30837649


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