NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States of America; Department of Neurology, University of Michigan, Ann Arbor, MI, United States of America.
NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States of America.
Neurobiol Dis. 2022 Aug;170:105766. doi: 10.1016/j.nbd.2022.105766. Epub 2022 May 16.
Dementia is a complex set of disorders affecting normal cognitive function. Recently, several clinical studies have shown that diabetes, obesity, and components of the metabolic syndrome (MetS) are associated with cognitive impairment, including dementias such as Alzheimer's disease. Maintaining normal cognitive function is an intricate process involving coordination of neuron function with multiple brain glia. Well-orchestrated bioenergetics is a central requirement of neurons, which need large amounts of energy but lack significant energy storage capacity. Thus, one of the most important glial functions is to provide metabolic support and ensure an adequate energy supply for neurons. Obesity and metabolic disease dysregulate glial function, leading to a failure to respond to neuron energy demands, which results in neuronal damage. In this review, we outline evidence for links between diabetes, obesity, and MetS components to cognitive impairment. Next, we focus on the metabolic crosstalk between the three major glial cell types, oligodendrocytes, astrocytes, and microglia, with neurons under physiological conditions. Finally, we outline how diabetes, obesity, and MetS components can disrupt glial function, and how this disruption might impair glia-neuron metabolic crosstalk and ultimately promote cognitive impairment.
痴呆症是一组影响正常认知功能的复杂疾病。最近，几项临床研究表明，糖尿病、肥胖症和代谢综合征（MetS）的组成部分与认知障碍有关，包括阿尔茨海默病等痴呆症。保持正常的认知功能是一个复杂的过程，涉及神经元功能与多种脑胶质细胞的协调。协调良好的生物能量是神经元的核心要求，神经元需要大量的能量，但缺乏显著的能量储存能力。因此，胶质细胞的最重要功能之一是为神经元提供代谢支持，并确保有充足的能量供应。肥胖和代谢疾病会扰乱胶质细胞的功能，导致无法响应神经元的能量需求，从而导致神经元损伤。在这篇综述中，我们概述了糖尿病、肥胖症和 MetS 成分与认知障碍之间的联系证据。接下来，我们重点介绍在生理条件下三种主要的神经胶质细胞类型（少突胶质细胞、星形胶质细胞和小胶质细胞）与神经元之间的代谢串扰。最后，我们概述了糖尿病、肥胖症和 MetS 成分如何破坏胶质细胞的功能，以及这种破坏如何损害胶质细胞-神经元代谢串扰，并最终促进认知障碍。
