组织素乙化恒温的破坏在实验糖尿病中触发了认知功能障碍
Aanchal Aggarwal1, Binduma Yadav2, Nishtha Sharma1
1National Agri-Food Biotechnology Institute, Knowledge City, Sector-81, SAS Nagar, Punjab, India.
Neurochemistry international
|August 20, 2023
概括
糖尿病通过表观遗传变化损害认知功能,特别是在大脑中减少了素乙化. 这项研究揭示了基因组脱乙酶 (HDAC) 活性升高有助于糖尿病小鼠的记忆力缺陷.
科学领域:
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 糖尿病 (第一类和第二类) 与中枢神经系统 (CNS) 的并发症有关,包括认知功能障碍.
- 潜在的表观遗传机制,特别是基因素乙化,导致糖尿病诱导的认知衰退仍然不太了解.
研究的目的:
- 在1型和2型糖尿病小鼠模型中调查素乙化和脱乙化在认知功能障碍中的作用.
- 探索改变表观遗传修饰对与记忆相关的基因表达的影响以及针对治疗干预的向激素脱乙酶 (HDAC) 活性的潜力.
主要方法:
- 在小鼠中诱导1型和2型糖尿病,然后对糖尿病参数进行评估.
- 使用行为测试评估认知表现:莫里斯水迷宫,新型物体识别和Y迷宫.
- 基因素乙化/脱乙化概况,HAT/HDAC活性测定,以及在大脑区域 (皮质,海马体) 特定HDAC的蛋白质/mRNA表达分析.
- 使用Trichostatin A (TSA) 对HDAC活性进行药理抑制,以评估其对认知功能和基因表达的影响.
主要成果:
- 与对照组相比,糖尿病小鼠 (T1D和T2D) 呈现出显著的认知缺陷.
- 在糖尿病小鼠的皮质和海马体中观察到H3K9/14和H4K12乙化显著下降.
- 升高的基因组脱乙酶 (HDAC) 活性,特别是增加HDAC 2和HDAC 3的表达,与降低的基因组乙化相关.
- 降低乙化与记忆相关基因 (BDNF,SYP,PSD-95) 的转录抑制有关.
- 用TSA对HDAC的药理抑制改善了认知障碍,并恢复了与记忆相关的基因的表达.
结论:
- 表观遗传失调,其特点是由于增加的HDAC活性而降低了基因素乙化,在与糖尿病相关的认知功能障碍中起着至关重要的作用.
- 针对HDACs是一个有前途的治疗策略,可以缓解糖尿病患者的记忆缺陷.
- 这项研究提供了对糖尿病相关记忆障碍背后的分子机制的关键见解,为新的治疗开发铺平了道路.
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