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.

Details

Title
ALDH1A1 regulates postsynaptic μ–opioid receptor expression in dorsal striatal projection neurons and mitigates dyskinesia through transsynaptic retinoic acid signaling
Author
Pan, Jing 1 ; Yu, Jia 2 ; Sun, Lixin 3 ; Xie Chengsong 3 ; Chang, Lisa 3 ; Wu, Junbing 3 ; Hawes, Sarah 3 ; Saez–Atienzar Sara 3 ; Wang, Zheng 4 ; Kung, Justin 5 ; Ding Jinhui 6   VIAFID ORCID Logo  ; Le, Weidong 7 ; Chen Shengdi 8 ; Cai Huaibin 3   VIAFID ORCID Logo 

1  Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Department of Neurology, Shanghai, P. R. China (GRID:grid.412277.5) (ISNI:0000 0004 1760 6738); National Institutes of Health, Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
2  Beijing Geriatric Hospital, Beijing University of Chinese Medicine, Institute for Geriatrics and Rehabilitation, Beijing, P. R. China (GRID:grid.24695.3c) (ISNI:0000 0001 1431 9176) 
3  National Institutes of Health, Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
4  National Institutes of Health, Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); Children’s National Medical Center, Washington, USA (GRID:grid.239560.b) (ISNI:0000 0004 0482 1586) 
5  National Institutes of Health, Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); University of Maryland, School of Medicine, Baltimore, USA (GRID:grid.411024.2) (ISNI:0000 0001 2175 4264) 
6  National Institute on Aging, National Institutes of Health, Bioinformatics Core, Laboratory of Neurogenetics, Bethesda, USA (GRID:grid.419475.a) (ISNI:0000 0000 9372 4913) 
7  the First Affiliated Hospital, Dalian Medical University, Clinical Research Center on Neurological Diseases, Dalian, P. R. China (GRID:grid.452435.1) 
8  Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Department of Neurology, Shanghai, P. R. China (GRID:grid.412277.5) (ISNI:0000 0004 1760 6738) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-40326-x
ProQuest document ID
2188210460
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.