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.

运动功能障碍是自闭症谱系障碍 (ASD) 患者的常见合并症。整个关键时期的小脑发育异常可能会影响运动功能并导致运动障碍。维生素 A (VA) 在神经系统的发育过程中起着至关重要的作用。然而，VA 缺乏 (VAD) 和 ASD 与运动功能障碍的相关性尚不清楚。因此，我们基于丙戊酸（VPA）治疗的自闭症模型建立了具有不同VA水平的大鼠模型。与具有正常 VA 水平（VA 正常，VAN）的 ASD 大鼠相比，患有 VAD 的 ASD 大鼠表现出加重的运动协调异常、浦肯野细胞丢失和浦肯野细胞的树突树枝状结构受损。此外，维A相关孤儿受体α（RORα）和维甲酸受体α（RARα）在VAD组ASD大鼠小脑中的表达水平低于ASD组VAN组。VA 补充剂 (VAS) 有效改善了患有 VAD 的 ASD 大鼠的运动协调和小脑浦肯野细胞异常。此外，染色质免疫沉淀 (ChIP) 测定的结果证实，在小脑的 RORα 启动子上检测到 RARα 的富集，并且 VAS 可以上调 RARα 对 RORα 启动子的结合能力。这些结果表明，自闭症患者的 VAD 可能导致小脑损伤，并且是加重 ASD 亚型与运动合并症的一个因素。VAS对自闭症运动障碍和浦肯野神经元损伤的治疗作用可能是由于RARα对RORα的调节。