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肥胖加快了与年龄相关的记忆缺陷,并改变了Ldlr-/-.Leiden小鼠白质通道的完整性

Florine Seidel^1,2, Martine C Morrison², Ilse Arnoldussen¹

¹Department Medical Imaging, Anatomy, Radboud Alzheimer Center, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Geert Grooteplein 21N, 6525 EZ, Nijmegen, the Netherlands.

Brain, behavior, & immunity - health

|April 28, 2025

概括

成年期中期的肥胖会通过影响大脑结构和功能来加速认知衰退. 在小鼠中,高脂肪饮食会恶化记忆力缺陷,改变大脑血流和白质完整性.

科学领域:

神经科学是一个神经科学.
代谢研究研究代谢研究
老龄化研究研究.

背景情况:

成年期中期的肥胖与加速的大脑衰老和认知障碍有关.
了解肥胖引起的特定大脑变化至关重要,但由于缺乏合适的翻译模型而受到限制.

研究的目的:

在转化小鼠模型中研究衰老和高脂肪饮食 (HFD) 诱导的肥胖对大脑结构,功能和认知的影响.
为了确定与肥胖相关的认知功能障碍相关的潜在大脑病理.

主要方法:

利用Ldlr-/.Leiden小鼠,作为肥胖和并发病的模型.
监测大脑结构和功能 (海马体积,皮质厚度,白质完整性,大脑血流,静止状态功能连接) 使用磁共振成像从3到8个月的年龄.
通过组织病理学和基因表达分析评估认知功能和检查大脑病理学.

主要成果:

老龄化Ldlr-/-.Leiden小鼠表现出与年龄相关的皮质厚度,大脑血流,大脑连接,神经发生和记忆的下降,以及神经炎症.
食HFD加速了记忆缺陷,并导致大脑血液流量增加,白质完整性降低 (微分异性质).
基因表达分析揭示了与年龄相关的代谢/神经元功能抑制和HFD诱导的神经炎症通路的激活.

结论:

Ldlr-/-.Leiden小鼠复制了在人类中观察到的关键与年龄相关的大脑变化.
在这个模型中,HFD养会通过破坏大脑 perfusion 和白质完整性来加剧认知衰退,突出显示肥胖对老化大脑的有害影响.

关键词:

衰老的衰老衰老的衰老认知障碍认知障碍是一种认知障碍.神经退行发生神经退行.神经成像是一种神经成像.肥胖问题肥胖问题

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