增加甲状腺激素作用通过降低神经元I型干扰素信号传递/糖尿病相关认知功能障碍的亡来缓解海马体损伤
Ling Tian1,2, Xing Li1,2,3, Xiaojiao Zeng1,2
1NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
概括
甲状腺功能障碍会恶化糖尿病相关认知功能障碍 (DACD). 利沃甲氧氨酸 (L-T4) 治疗通过优化甲状腺激素 (TH) 信号传递和抑制干扰素I信号传递诱导的亡,改善了DACD小鼠的认知功能.
科学领域:
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 甲状腺功能障碍与糖尿病相关的认知功能障碍 (DACD) 有关.
- 在DACD大脑内甲状腺激素 (TH) 信号传递和作用的变化尚未得到充分理解.
研究的目的:
- 研究DACD小鼠大脑中TH信号传递和作用的变化.
- 探索莱沃西 (L-T4) 治疗对DACD的神经保护作用.
主要方法:
- 使用KK-Ay小鼠作为2型糖尿病模型,用L-T4或盐水治疗.
- 通过行为测试 (开放场,莫里斯水迷宫) 评估认知和记忆功能.
- 评估了海马TH信号传递,RNA测序,qPCR,西部斑点,免疫光学和多重免疫组织化学.
主要成果:
- DACD小鼠表现出改变的海马TH载体,神酶,TH受体和TH调节基因.
- 通过优化TH信号传递,L-T4治疗部分恢复了认知功能和海马神经元活动.
- L-T4治疗抑制了I型干扰素 (IFN-I) 信号传递和亡途径,这些途径与海马体损伤有关.
结论:
- 在DACD中显现出异常的海马TH信号和作用.
- 外源L-T4通过抑制IFN-I信号诱导的亡来改善DACD中的海马损伤.
- 这项研究突出了一个新的治疗目标,用于管理糖尿病患者的认知缺陷.
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