Involvement of retinoic acid receptor α in the autistic-like behavior of rats with vitamin A deficiency by regulating neurexin 1 in the visual cortex: a mechanism study
LI Li-Sha, ZHANG Qian, LIU Huan, WU Qiong-Hui, YANG Ting, CHEN Jie, LI Ting-Yu
Department of Child Health Care, Children's Hospital of Chongqing Medical University/National Clinical Research Center for Child Health and Disorders/Ministry of Education Key Laboratory of Child Development and Disorders/Chongqing Key Laboratroy of Child Nutrition and Health, Chongqing 400014, China
Abstract：Objective To study the mechanism of retinoic acid receptor α (RARα) signal change to regulate neurexin 1 (NRXN1) in the visual cortex and participate in the autistic-like behavior in rats with vitamin A deficiency (VAD). Methods The models of vitamin A normal (VAN) and VAD pregnant rats were established, and some VAD maternal and offspring rats were given vitamin A supplement (VAS) in the early postnatal period. Behavioral tests were performed on 20 offspring rats in each group at the age of 6 weeks. The three-chamber test and the open-field test were used to observe social behavior and repetitive stereotyped behavior. High-performance liquid chromatography was used to measure the serum level of retinol in the offspring rats in each group. Electrophysiological experiments were used to measure the long-term potentiation (LTP) level of the visual cortex in the offspring rats. Quantitative real-time PCR and Western blot were used to measure the expression levels of RARα, NRXN1, and N-methyl-D-aspartate receptor 1 (NMDAR1). Chromatin co-immunoprecipitation was used to measure the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene. Results The offspring rats in the VAD group had autistic-like behaviors such as impaired social interactions and repetitive stereotypical behaviors, and VAS started immediately after birth improved most of the behavioral deficits in offspring rats. The offspring rats in the VAD group had a significantly lower serum level of retinol than those in the VAN and VAS groups (P<0.05). Compared with the offspring rats in the VAN and VAS groups, the offspring rats in the VAD group had significant reductions in the mRNA and protein expression levels of NMDAR1, RARα, and NRXN1 and the LTP level of the visual cortex (P<0.05). The offspring rats in the VAD group had a significant reduction in the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene in the visual cortex compared with those in the VAN and VAS groups (P<0.05). Conclusions RARα affects the synaptic plasticity of the visual cortex in VAD rats by regulating NRXN1, thereby participating in the formation of autistic-like behaviors in VAD rats.
LI Li-Sha,ZHANG Qian,LIU Huan et al. Involvement of retinoic acid receptor α in the autistic-like behavior of rats with vitamin A deficiency by regulating neurexin 1 in the visual cortex: a mechanism study[J]. CJCP, 2022, 24(8): 928-935.
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