Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Neuroendocrinol. 2012 Aug;24(8):1120-5. doi: 10.1111/j.1365-2826.2012.02327.x.
Recent epidemiological studies demonstrate that obesity is related to a high incidence of cognitive impairment. In the present study, cognitive behaviours in diet-induced obese (DIO) mice fed 60% high-fat diet for 16 weeks were compared with those in mice fed a control diet (CD) in fear-conditioning tests including both contextual and cued elements that preferentially depend on the hippocampus and amygdala, respectively. Furthermore, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) content in the brain areas was examined in both CD and DIO mice. In fear-conditioning tests, the freezing percentages of both contextual fear and cued fear responses in DIO mice were significantly lower than in CD mice. BDNF content in the cerebral cortex and hippocampus of DIO mice was significantly lower than that in CD mice. Its receptor, full-length TrkB, in the amygdala of DIO mice was significantly decreased compared to that in CD mice, although not in the cerebral cortex, hippocampus and hypothalamus. By contrast, NT-3 content in the hippocampus, amygdala and hypothalamus of DIO mice was significantly higher than that in CD mice. Its receptor, full-length TrkC, was not significantly different between CD and DIO mice. The present study demonstrates that DIO mice show impairment of both hippocampus-dependent contextual and amygdala-dependent cued responses in the fear-conditioning tests, as well as an imbalance in the interaction between the BDNF and NT-3 systems in the cerebral cortex, hippocampus and amygdala related to cognition and fear.
最近的流行病学研究表明，肥胖与认知障碍的高发率有关。在本研究中，比较了喂食 60%高脂肪饮食 16 周的饮食诱导肥胖（DIO）小鼠与喂食对照饮食（CD）的小鼠在包括上下文和提示元素的恐惧条件反射测试中的认知行为，这两种元素分别优先依赖于海马体和杏仁核。此外，还检查了 CD 和 DIO 小鼠大脑区域中的脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3）含量。在恐惧条件反射测试中，DIO 小鼠的上下文恐惧和提示恐惧反应的冻结百分比明显低于 CD 小鼠。DIO 小鼠大脑皮层和海马体中的 BDNF 含量明显低于 CD 小鼠。其受体全长 TrkB 在 DIO 小鼠的杏仁核中明显低于 CD 小鼠，尽管在大脑皮层、海马体和下丘脑则没有。相比之下，DIO 小鼠的海马体、杏仁核和下丘脑的 NT-3 含量明显高于 CD 小鼠。其受体全长 TrkC 在 CD 和 DIO 小鼠之间没有显著差异。本研究表明，DIO 小鼠在恐惧条件反射测试中表现出海马体依赖的上下文和杏仁核依赖的提示反应受损，以及与认知和恐惧相关的大脑皮层、海马体和杏仁核中 BDNF 和 NT-3 系统相互作用失衡。
