Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function

被引:207
作者
Bocarsly, Miriam E. [1 ,2 ]
Fasolino, Maria [1 ,2 ]
Kane, Gary A. [1 ,2 ]
LaMarca, Elizabeth A. [1 ,2 ]
Kirschen, Gregory W. [1 ,2 ]
Karatsoreos, Ilia N. [3 ,4 ]
McEwen, Bruce S. [4 ]
Gould, Elizabeth [1 ,2 ]
机构
[1] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA
[2] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA
[3] Washington State Univ, Dept Integrat Physiol & Neurosci, Pullman, WA 99164 USA
[4] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA
关键词
obesity; prefrontal cortex; cognition; dendritic spine; microglia; MEDIAL PREFRONTAL CORTEX; BODY-MASS INDEX; LONG-TERM POTENTIATION; METABOLIC SYNDROME; PYRAMIDAL NEURONS; BRAIN; PERFORMANCE; GLUCOCORTICOIDS; ORGANIZATION; ASSOCIATION;
D O I
10.1073/pnas.1511593112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Obesity is a major public health problem affecting overall physical and emotional well-being. Despite compelling data suggesting an association between obesity and cognitive dysfunction, this phenomenon has received relatively little attention. Neuroimaging studies in obese humans report reduced size of brain regions involved in cognition, but few studies have investigated the cellular processes underlying cognitive decline in obesity or the influence of obesity on cognition in the absence of obesity-related illnesses. Here, a rat model of diet-induced obesity was used to explore changes in brain regions important for cognition. Obese rats showed deficits on cognitive tasks requiring the prefrontal and perirhinal cortex. Cognitive deficits were accompanied by decreased dendritic spine density and synaptic marker expression in both brain regions. Microglial morphology was also changed in the prefrontal cortex. Detrimental changes in the prefrontal cortex and perirhinal cortex occurred before metabolic syndrome or diabetes, suggesting that these brain regions may be particularly vulnerable to early stage obesity.
引用
收藏
页码:15731 / 15736
页数:6
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