ALDH1A1 regulates postsynaptic µ-opioid receptor expression in dorsal striatal projection neurons and mitigates dyskinesia through transsynaptic retinoic acid signaling.
Sci Rep
; 9(1): 3602, 2019 03 05.
Article
en En
| MEDLINE
| ID: mdl-30837649
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Tretinoina
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Receptores Opioides mu
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Proteínas de Homeodominio
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Cuerpo Estriado
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Discinesias
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Retinal-Deshidrogenasa
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Neuronas Dopaminérgicas
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Familia de Aldehído Deshidrogenasa 1
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2019
Tipo del documento:
Article