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牛磺酸通过 PTEN/mTOR/AKT 信号通路改善 BTBR 小鼠的自闭症样行为和海马神经发生缺陷。

Taurine Improved Autism-Like Behaviours and Defective Neurogenesis of the Hippocampus in BTBR Mice through the PTEN/mTOR/AKT Signalling Pathway.

机构信息

Department of Child Health, Shenzhen Guangming Women and Child Healthcare Hospital, Shenzhen, China.

出版信息

Folia Biol (Praha). 2024;70(1):45-52. doi: 10.14712/fb2024070010045.

Abstract

Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined the mechanism of taurine effect on hippocampal neurogenesis in genetically inbred BTBR T+ tf/J (BTBR) mice, a proposed model of ASD. In this ASD mouse model, we explored the effect of oral taurine supplementation on ASD-like behaviours in an open field test, elevated plus maze, marble burying test, self-grooming test, and three-chamber test. The mice were divided into four groups of normal controls (WT) and models (BTBR), who did or did not receive 6-week taurine supplementation in water (WT, WT+ Taurine, BTBR, and BTBR+Taurine). Neurogenesis-related effects were determined by Ki67 immunofluorescence staining. Western blot analysis was performed to detect the expression of phosphatase and tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that taurine improved the autism-like behaviour, increased the proliferation of hippocampal cells, promoted PTEN expression, and reduced phosphorylation of mTOR and AKT in hippocampal tissue of the BTBR mice. In conclusion, taurine reduced the autism-like behaviour in partially inherited autism model mice, which may be associa-ted with improving the defective neural precursor cell proliferation and enhancing the PTEN-associated pathway in hippocampal tissue.

摘要

目前,仍缺乏对自闭症谱系障碍(ASD)患者的有效治疗方法。牛磺酸对 ASD 模型动物的自闭症样行为表现出治疗作用。在这里,我们确定了牛磺酸对遗传同窝 BTBR T+ tf/J(BTBR)小鼠(一种拟 ASDs 模型)海马神经发生的作用机制。在这种 ASD 小鼠模型中,我们通过旷场测试、高架十字迷宫测试、滚球掩埋测试、自我梳理测试和三箱测试,探究了口服牛磺酸补充对 ASD 样行为的影响。将小鼠分为四组:正常对照组(WT)和模型组(BTBR),每组再分为接受或不接受牛磺酸补充的两个亚组(WT、WT+Taurine、BTBR 和 BTBR+ Taurine)。通过 Ki67 免疫荧光染色确定神经发生相关作用。通过 Western blot 分析检测磷酸酶和张力蛋白同源物缺失的染色体 10(PTEN)/mTOR/AKT 通路相关蛋白的表达。结果表明,牛磺酸改善了自闭症样行为,增加了海马细胞的增殖,促进了 BTBR 小鼠海马组织中 PTEN 的表达,并降低了 mTOR 和 AKT 的磷酸化。总之,牛磺酸减少了部分遗传性自闭症模型小鼠的自闭症样行为,这可能与改善神经前体细胞增殖缺陷和增强海马组织中与 PTEN 相关的通路有关。

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