Vitamin A deficiency exacerbates autism-like behaviors and abnormalities of the enteric nervous system in a valproic acid-induced rat model of autism

Autor: Si Wang, Ting Yang, Jie Chen, Huan Liu, Jiang Zhu, Tingyu Li, Boli Cheng, Qionghui Wu, Xin-Hui Zhang
Rok vydání: 2020
Předmět:
medicine.medical_specialty
Toxicology
behavioral disciplines and activities
Enteric Nervous System
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Risk Factors
Internal medicine
parasitic diseases
mental disorders
medicine
Animals
Autistic Disorder
Vitamin A
030304 developmental biology
0303 health sciences
Valproic Acid
Behavior
Animal
business.industry
Vitamin A Deficiency
General Neuroscience
Retinoic Acid Receptor alpha
Proto-Oncogene Proteins c-ret
medicine.disease
Vitamin A deficiency
Intestines
Retinoic acid receptor
Disease Models
Animal
Endocrinology
medicine.anatomical_structure
Autism spectrum disorder
Peripheral nervous system
Autism
Enteric nervous system
Signal transduction
business
Gastrointestinal Motility
030217 neurology & neurosurgery
medicine.drug
Zdroj: Neurotoxicology. 79
ISSN: 1872-9711
Popis: The manifestations of autism spectrum disorder (ASD) are highly heterogeneous. As many individuals with ASD have gastrointestinal (GI) comorbidities, ASD with GI problems is considered to be a subtype of ASD. Vitamin A (VA) plays an important role in the development of both the central and peripheral nervous system. However, the relationship between VA deficiency (VAD) and ASD with GI comorbidities is still unclear. We established rat models with different VA levels based on the valproic acid-induced autism model. Compared to autism model rats with VA normal (VAN), autism model rats with gestational VAD showed more severe autism-like behavior, increased GI transit time, and impairment of the enteric nervous system (ENS). Besides, the expression levels of retinoic acid receptor α (RARα) and Ret in autism model rats with VAD were decreased compared with those in rats with VAN. Supplementation with VA was found to effectively ameliorate autism-like behaviors and impairments of GI motility and the ENS in autism model rats with VAD. Chromatin immunoprecipitation results suggested that RARa can bind to the promoter region of the Ret gene and regulate the Ret signaling pathway. We speculate that VAD in autism might lead to impairments of both the brain and ENS. VAD might be a factor that causes individuals to be more susceptible to ASD-related risk factors and aggravates a subtype of ASD with GI comorbidities.
Databáze: OpenAIRE
Externí odkaz: