The Liver X Receptor Agonist TO901317 Ameliorates Behavioral Deficits in Two Mouse Models of Autism
The Liver X Receptor Agonist TO901317 Ameliorates Behavioral Deficits in Two Mouse Models of Autism
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肝脏 X 受体激动剂 TO901317 可改善两种自闭症小鼠模型的行为缺陷
DOI：
10.3389/fncel.2019.00213
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发表时间：
2019-05-14
影响因子：
5.3
通讯作者：
Fan, Xiaotang
中科院分区：
文献类型：
--
作者：
Cai, Yulong;Zhong, Hongyu;Fan, Xiaotang
自闭症谱系障碍（ASD）是一种以社会缺陷和重复刻板行为为特征的发育障碍。目前没有药物可用于治疗ASD的核心症状，这表明迫切需要新的治疗策略。自闭症的神经生物学是复杂的，但新兴的研究表明，海马神经发生的缺陷与ASD的人类和小鼠模型中的ASD相关，这表明恢复神经发生可能是ASD的一种新的治疗方法。在此，我们发现，出生后给予TO 901317（TO），一种有效的肝脏X受体（LXR）激动剂，通常激活海马中的LXRβ及其靶基因，并减轻BTBR T+ tf/J（BTBR）和丙戊酸（VPA）诱导的小鼠模型中的社会缺陷和刻板行为。此外，我们进一步证实，TO产后治疗也挽救了这两个模型中成年海马神经发生的抑制。总之，我们的研究表明，LXR激动剂靶向海马神经发生可能是一种新的潜在的治疗ASD。
Autism spectrum disorder (ASD) is a developmental disability characterized by social deficits and repetitive stereotyped behaviors. There are currently no drugs available for the treatment of the core symptoms of ASD, suggesting an urgent need for new therapeutic strategies. The neurobiology of autism is complex, but emerging research indicates that defects in hippocampal neurogenesis are associated with ASD in both humans and mouse models of ASD, leading to the suggestion that restoring neurogenesis may be a novel therapeutic approach for ASD. Here, we found that postnatal treatment with TO901317 (TO), a potent liver X receptor (LXR) agonist, typically activated LXRβ and its target genes in the hippocampus, and alleviated the social deficits and stereotypical behaviors in BTBR T+ tf/J (BTBR) and valproic acid (VPA)-induced mouse models. In addition, we further confirmed that TO postnatal treatment also rescued the inhibition of adult hippocampal neurogenesis in these two models. In summary, our study suggests that LXR agonist targeting hippocampal neurogenesis may represent a novel potential therapy for ASD.