Vitamin A supplementation ameliorates motor incoordination via modulating RORα in the cerebellum in a valproic acid-treated rat autism model with vitamin A deficiency
| Autor: | Tingyu Li, Boli Cheng, Huan Liu, Nali Hou, Qionghui Wu, Si Wang, Lisha Li, Ting Yang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Cerebellum medicine.medical_specialty Purkinje cell Cerebellar Purkinje cell Toxicology behavioral disciplines and activities Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Pregnancy Internal medicine mental disorders medicine Animals Autistic Disorder Vitamin A 030304 developmental biology 0303 health sciences Valproic Acid Vitamin A Deficiency business.industry General Neuroscience Nuclear Receptor Subfamily 1 Group F Member 1 medicine.disease Rats Motor coordination Vitamin A deficiency Retinoic acid receptor medicine.anatomical_structure Endocrinology Prenatal Exposure Delayed Effects Autism Female business Psychomotor Performance 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | NeuroToxicology. 85:90-98 |
| ISSN: | 0161-813X |
| DOI: | 10.1016/j.neuro.2021.05.004 |
| Popis: | Motor dysfunctions are common comorbidities among autism spectrum disorder (ASD) patients. Abnormal cerebellar development throughout critical periods may have an effect on motor functions and result in motor impairments. Vitamin A (VA) plays a crucial role in the developing process of the nervous system. The correlation of VA deficiency (VAD) and ASD with motor dysfunctions, however, is not clear. Therefore, we built rat models with different VA levels based on the valproic acid (VPA)-treated autism model. ASD rats with VAD showed aggravated motor coordination abnormalities, Purkinje cell loss and impaired dendritic arborization of Purkinje cells compared to ASD rats with normal VA levels (VA normal, VAN). Additionally, the expression levels of retinoid-related orphan receptor α (RORα) and retinoic acid receptor α (RARα) were lower in the cerebellum of ASD rats with VAD than in those of ASD rats with VAN. VA supplementation (VAS) effectively improved motor coordination and cerebellar Purkinje cell abnormalities in ASD rats with VAD. Furthermore, the results of chromatin immunoprecipitation (ChIP) assays confirmed that the enrichment of RARα was detected on the RORα promoter in the cerebellum and that VAS could upregulate the binding capacity of RARα for RORα promoters. These results showed that VAD in autism might result in cerebellar impairments and be a factor aggravating a subtype of ASD with motor comorbidities. The therapeutic effect of VAS on motor deficits and Purkinje neuron impairments in autism might be due to the regulation of RORα by RARα. |
| Databáze: | OpenAIRE |
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