通过调节BDNF/NF-κB/GSK-3β通路,DCI可以改善糖尿病脑病变
Haizhu Zhang1, Xiao Han1, Zhuoting Zhu1
1School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, Hebei, PR China; Hebei Key Laboratory for Chronic Diseases, Tangshan 063210, Hebei, PR China.
Experimental neurology
|April 5, 2025
概括
在糖尿病脑病变 (DE) 鼠标模型中,D-chiral inositol (DCI) 改善了认知功能和大脑健康. DCI调节了关键信号通路,为DE提供了潜在的治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 糖尿病脑病变 (DE) 导致认知能力下降和与糖尿病相关的大脑变化.
- 目前对ED的治疗方法有限,这凸显了对新型治疗方法的需求.
- 一种饮食化合物D-chiral inositol (DCI) 显示出潜在的低血糖和抗炎性质,但其对DE的影响仍然未被探索.
研究的目的:
- 在糖尿病脑病变 (DE) 的小鼠模型中研究D-chiral inositol (DCI) 的治疗潜力.
- 阐明DCI可能缓解DE相关的神经病理和认知缺陷的潜在分子机制.
主要方法:
- 雄性db/db小鼠,一种2型糖尿病和DE的模型,被DCI (35和70 mg/kg/day) 治疗了8周.
- 用莫里斯水迷宫测试来评估认知功能.
- 分析了海马和皮层组织的病理变化 (HE和Nissl染色) 和与突触功能,炎症,细胞亡和神经纤维细胞结相关的分子变化 (qRT-PCR,免疫组织化学,西部斑点).
主要成果:
- 在db/db小鼠中,DCI治疗显著改善了学习和记忆.
- 组织学分析显示,DCI治疗小鼠的海马体和皮质中神经元损失和pyknosis减少.
- DCI使突触蛋白水平 (PSD95,SYN) 正常化,并调节了炎症和亡标志物.
- 分子分析表明,DCI增加了BDNF,IκB-α和p-GSK-3β (Ser9) 的表达,同时降低了NF-κB p65,p-GSK3 (Y216+Y279),P-Tau (Thr231) 和P-Tau (Ser396).
结论:
- D-chiral inositol (DCI) 在糖尿病脑病变 (DE) 的小鼠模型中显示出神经保护作用和认知益处.
- 似乎DCI通过调节BDNF/NF-κB/GSK-3β信号通路来发挥其治疗作用.
- 这些发现表明,DCI作为治疗糖尿病脑病变的潜在治疗剂具有前途.
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