Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate (NaPB) is a well-known long-term treatment of urea cycle disorders in children. In this study, we assessed the therapeutic effects of NaPB, which is a chemical chaperone as well as histone deacetylase inhibitor on a BTBR T + Itpr3tf/J (BTBR) mice model of ASD. We found that acute and chronic treatment of NaPB remarkably improved, not only core ASD symptoms, including repetitive behaviors and sociability deficit, but also cognitive impairment in the BTBR mice. NaPB substantially induced histone acetylation in the brain of the BTBR mice. Intriguingly, the therapeutic effects of NaPB on autistic-like behaviors, such as repetitive behaviors, impaired sociability, and cognitive deficit also showed in the valproic acid (VPA)–induced mouse model of autism. In addition, pentylenetetrazole (PTZ)-induced seizure was significantly attenuated by NaPB treatment in C57BL/6J and BTBR mice. These findings suggest that NaPB may provide a novel therapeutic approach for the treatment of patients with ASD.

自闭症谱系障碍（ASD）是一种神经发育障碍，其特征在于社交互动不足以及行为的限制性，重复性和刻板印象。但是，目前没有针对这些核心ASD症状的药物。苯丁酸钠（NaPB）是儿童尿素循环障碍的长期治疗方法。在这项研究中，我们评估了NaPB（一种化学分子伴侣和组蛋白脱乙酰基酶抑制剂）对ASD的BTBR T + Itpr3tf / J（BTBR）小鼠模型的治疗效果。我们发现，NaPB的急性和慢性治疗不仅改善了ASD的核心症状，包括重复行为和社交能力缺陷，而且还显着改善了BTBR小鼠的认知功能。NaPB实质上在BTBR小鼠的大脑中诱导组蛋白乙酰化。有趣的是 丙戊酸（VPA）诱发的小鼠自闭症模型也显示出NaPB对自闭症样行为（例如重复行为，社交能力受损和认知缺陷）的治疗作用。此外，在C57BL / 6J和BTBR小鼠中，NaPB处理可显着减轻戊四唑（PTZ）诱导的癫痫发作。这些发现表明，NaPB可能为ASD患者提供一种新颖的治疗方法。