Impaired fear extinction retention and increased anxiety-like behaviours induced by limited daily access to a high-fat/high-sugar diet in male rats: Implications for diet-induced prefrontal cortex dysregulation
Impaired fear extinction retention and increased anxiety-like behaviours induced by limited daily access to a high-fat/high-sugar diet in male rats: Implications for diet-induced prefrontal cortex dysregulation
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DOI：
10.1016/j.nlm.2016.10.002
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发表时间：
2016-12-01
影响因子：
2.7
通讯作者：
Reichelt, Amy C.
中科院分区：
文献类型：
--
作者：
Baker, Kathryn D.;Reichelt, Amy C.
焦虑症和肥胖症在青年和年轻人中都很常见。尽管越来越多的证据表明，过度食用可口的高脂肪/高糖“垃圾”食品会导致不良的神经认知结果，但人们对可口饮食对情绪记忆和恐惧调节的影响知之甚少。在本实验中，我们研究了在青春期每天2小时摄入高脂肪/高糖（HFHS）食物对年轻成年大鼠恐惧抑制和焦虑样行为的影响。暴露于HFHS饮食的大鼠表现出受损的保留恐惧消退和增加焦虑样行为在出现测试相比，大鼠喂养的标准饮食。HFHS喂养的大鼠表现出饮食诱导的前额叶皮层（PFC）功能的变化，这是通过改变GABA能小清蛋白表达抑制性中间神经元和稳定的转录因子Delta FosB的表达来检测的，该转录因子Delta FosB在PFC中积累以响应慢性刺激。免疫组织化学分析显示，动物喂HFHS饮食有较少的小白蛋白表达细胞和FosB/三角洲FosB表达水平增加的边缘下皮层，一个地区牵连在巩固的恐惧灭绝。有一个趋势增加IBA-1免疫反应，小胶质细胞活化的标志物，在inforimbic皮质HFHS饮食暴露后，但细胞外糖蛋白reelin的表达不受影响。这些发现表明，在青春期HFHS饮食与减少前额叶小白蛋白神经元和受损的恐惧抑制在成年期。HFHS饮食对恐惧调节机制的不利影响可能会使肥胖个体容易发展为焦虑症。(C)2016 Elsevier Inc. All rights reserved.
Anxiety disorders and obesity are both common in youth and young adults. Despite increasing evidence that over-consumption of palatable high-fat/high-sugar "junk" foods leads to adverse neurocognitive outcomes, little is known about the effects of palatable diets on emotional memories and fear regulation. In the present experiments we examined the effects of daily 2 h consumption of a high-fat/high-sugar (HFHS) food across adolescence on fear inhibition and anxiety-like behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired retention of fear extinction and increased anxiety-like behaviour in an emergence test compared to rats fed a standard diet. The HFHS-fed rats displayed diet induced changes in prefrontal cortex (PFC) function which were detected by altered expression of GABAergic parvalbumin-expressing inhibitory interneurons and the stable transcription factor Delta FosB which accumulates in the PFC in response to chronic stimuli. Immunohistochemical analyses of the medial PFC revealed that animals fed the HFHS diet had fewer parvalbumin-expressing cells and increased levels of FosB/Delta FosB expression in the infralimbic cortex, a region implicated in the consolidation of fear extinction. There was a trend towards increased IBA-1 immunoreactivity, a marker of microglial activation, in the infralimbic cortex after HFHS diet exposure but expression of the extracellular glycoprotein reelin was unaffected. These findings demonstrate that a HFHS diet during adolescence is associated with reductions of prefrontal parvalbumin neurons and impaired fear inhibition in adulthood. Adverse effects of HFHS diets on the mechanisms of fear regulation may precipitate a vulnerability in obese individuals to the development of anxiety disorders. (C) 2016 Elsevier Inc. All rights reserved.