视皮层神经连接蛋白 1 介导维生素 A 缺乏大鼠类自闭症行为与维甲酸受体 α 的关系：一项机制研究。
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.
机构信息
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.
出版信息
Zhongguo Dang Dai Er Ke Za Zhi. 2022 Aug 15;24(8):928-935. doi: 10.7499/j.issn.1008-8830.2204016.
OBJECTIVES
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 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 (<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 (<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 gene in the visual cortex compared with those in the VAN and VAS groups (<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.
目的
研究维甲酸受体α（RARα）信号变化调节视皮层神经连接蛋白 1（NRXN1）的机制，并探讨其在维生素 A 缺乏（VAD）大鼠自闭症样行为中的作用。
方法
建立维生素 A 正常（VAN）和 VAD 孕鼠模型，部分 VAD 孕鼠及其仔鼠于生后早期给予维生素 A 补充（VAS）。6 周龄时，每组各取 20 只仔鼠进行行为学测试，采用三箱测试和旷场测试观察其社会行为和刻板行为。采用高效液相色谱法检测各组仔鼠血清视黄醇水平。电生理实验检测仔鼠视皮层长时程增强（LTP）水平。实时定量 PCR 和 Western blot 检测 RARα、NRXN1 和 N-甲基-D-天冬氨酸受体 1（NMDAR1）的表达水平。染色质免疫共沉淀检测 RARα 转录因子在 基因启动子区的富集情况。
结果
VAD 组仔鼠出现社交障碍和刻板行为等自闭症样行为，生后立即开始 VAS 干预可改善仔鼠大部分行为缺陷。与 VAN 组和 VAS 组比较，VAD 组仔鼠血清视黄醇水平明显降低（<0.05）。与 VAN 组和 VAS 组比较，VAD 组仔鼠 NMDAR1、RARα、NRXN1 的 mRNA 和蛋白表达水平以及视皮层 LTP 水平明显降低（<0.05）。VAD 组仔鼠视皮层中 RARα 转录因子在 基因启动子区的富集明显低于 VAN 组和 VAS 组（<0.05）。
结论
RARα 通过调节 NRXN1 影响 VAD 大鼠视皮层的突触可塑性，从而参与 VAD 大鼠自闭症样行为的形成。
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