神经炎症
海马结构
促炎细胞因子
海马体
血脑屏障
内分泌学
星形胶质细胞
星形胶质增生
神经科学
内科学
神经化学
认知功能衰退
医学
生物
炎症
中枢神经系统
痴呆
疾病
作者
Gabriela Cristina de Paula,Henver S. Brunetta,Daiane F. Engel,Joana M. Gaspar,Lı́cio A. Velloso,David Engblom,Jade de Oliveira,Andreza Fabro de
标识
DOI:10.3389/fnins.2021.734158
摘要
Worldwide, and especially in Western civilizations, most of the staple diets contain high amounts of fat and refined carbohydrates, leading to an increasing number of obese individuals. In addition to inducing metabolic disorders, energy dense food intake has been suggested to impair brain functions such as cognition and mood control. Here we demonstrate an impaired memory function already 3 days after the start of a high-fat diet (HFD) exposure, and depressive-like behavior, in the tail suspension test, after 5 days. These changes were followed by reduced synaptic density, changes in mitochondrial function and astrocyte activation in the hippocampus. Preceding or coinciding with the behavioral changes, we found an induction of the proinflammatory cytokines TNF-α and IL-6 and an increased permeability of the blood-brain barrier (BBB), in the hippocampus. Finally, in mice treated with a TNF-α inhibitor, the behavioral and BBB alterations caused by HFD-feeding were mitigated suggesting that inflammatory signaling was critical for the changes. In summary, our findings suggest that HFD rapidly triggers hippocampal dysfunction associated with BBB disruption and neuroinflammation, promoting a progressive breakdown of synaptic and metabolic function. In addition to elucidating the link between diet and cognitive function, our results might be relevant for the comprehension of the neurodegenerative process.
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