Retinoic acid supplementation ameliorates motor incoordination via RARα-CBLN2 in the cerebellum of a prenatal valproic acid-exposed rat autism model.
Neurosci Lett
; 809: 137316, 2023 07 13.
Article
em En
| MEDLINE
| ID: mdl-37247722
ABSTRACT
In addition to their core symptoms, most individuals with autism spectrum disorder (ASD) also experience motor impairments. These impairments are often linked to the cerebellum, which is the focus of the current study. Herein, we utilized a prenatal valproic acid (VPA)-induced rat model of autism and performed RNA sequencing in the cerebellum. Relative to control animals, the VPA-treated offspring demonstrated both abnormal motor coordination and impaired dendritic arborization of Purkinje cells (PCs). Concurrently, we observed a decrease in the cerebellar expression of retinoic acid (RA) synthesis enzymes (RDH10, ALDH1A1), metabolic enzyme (CYP26A2), and lower levels of RA, retinoic acid receptor α (RARα), and Cerebellin2 (CBLN2) in the VPA-treated offspring. However, RA supplementation ameliorated these deficits, restoring motor coordination, normalizing PCs dendritic arborization, and increasing the expression of RA, RARα, and CBLN2. Further, ChIP assays confirmed that RA supplementation enhanced RARα's binding capacity to CBLN2 promoters. Collectively, these findings highlight the therapeutic potential of RA for treating motor incoordination in VPA-induced autism, acting through the RARα-CBLN2 pathway.
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Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
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Transtorno Autístico
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Transtorno do Espectro Autista
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article