Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid.
Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid.
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DOI：
10.1371/journal.pone.0116363
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Riesgo R
中科院分区：
文献类型：
--
作者：
Baronio D;Castro K;Gonchoroski T;de Melo GM;Nunes GD;Bambini-Junior V;Gottfried C;Riesgo R
自闭症谱系障碍 (ASD) 是一组神经发育障碍，主要特征是社交互动和沟通受损，以及重复行为和兴趣受限。组胺受体 3 (H3R) 配体被认为是治疗不同脑部疾病和认知障碍的潜在治疗剂。考虑到这一点，本研究的目的是评估环丙昔芬（CPX）（一种 H3R 拮抗剂）对产前暴露于丙戊酸（VPA）所致自闭症动物模型的作用。瑞士小鼠在胚胎第 11 天时在产前暴露于 VPA，并在生命 50 天时评估其社会行为、伤害性阈值和重复行为。每次行为测试前 30 分钟进行 CPX (3 mg/kg) 或盐水治疗。与用 CPX 治疗的 VPA 动物相比，VPA 组表现出较低的社交指数。与对照组相比，VPA 动物表现出明显更高的伤害性阈值，并且 CPX 治疗无法改变该参数。在弹珠埋藏测试中，VPA动物埋藏弹珠的数量与明显重复的行为一致。接受 CPX 的 VPA 动物埋藏的弹珠数量减少。总之，我们报告说，急性剂量的 CPX 能够减轻自闭症 VPA 模型中存在的社交缺陷和刻板印象。我们的研究结果有可能有助于研究自闭症谱系障碍的分子基础和改善自闭症谱系障碍症状的可能治疗方法，尽管仍需要更多的研究来证实和扩展这一初步数据。
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders primarily characterized by impaired social interaction and communication, and by restricted repetitive behaviors and interests. Ligands of histamine receptor 3 (H3R) are considered potential therapeutic agents for the treatment of different brain disorders and cognitive impairments. Considering this, the aim of the present study is to evaluate the actions of ciproxifan (CPX), an H3R antagonist, on the animal model of autism induced by prenatal exposure to valproic acid (VPA). Swiss mice were prenatally exposed to VPA on embryonic day 11 and assessed for social behavior, nociceptive threshold and repetitive behavior at 50 days of life. The treatment with CPX (3 mg/kg) or saline was administered 30 minutes before each behavioral test. The VPA group presented lower sociability index compared to VPA animals that were treated with CPX. Compared to the Control group, VPA animals presented a significantly higher nociceptive threshold, and treatment with CPX was not able to modify this parameter. In the marble burying test, the number of marbles buried by VPA animals was consistent with markedly repetitive behavior. VPA animals that received CPX buried a reduced amount of marbles. In summary, we report that an acute dose of CPX is able to attenuate sociability deficits and stereotypies present in the VPA model of autism. Our findings have the potential to help the investigations of both the molecular underpinnings of ASD and of possible treatments to ameliorate the ASD symptomatology, although more research is still necessary to corroborate and expand this initial data.
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