Modulation of Fear Memory by Dietary Polyunsaturated Fatty Acids via Cannabinoid Receptors
Modulation of Fear Memory by Dietary Polyunsaturated Fatty Acids via Cannabinoid Receptors
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DOI：
10.1038/npp.2014.32
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发表时间：
2014-02
影响因子：
7.6
通讯作者：
Daisuke Yamada;Jiro Takeo;P. Koppensteiner;K. Wada;M. Sekiguchi
中科院分区：
文献类型：
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作者：
Daisuke Yamada;Jiro Takeo;P. Koppensteiner;K. Wada;M. Sekiguchi
尽管潜在的机制尚不清楚，但几项研究表明，n-3长链多不饱和脂肪酸(PUFA)对焦虑症患者有好处。高度的恐惧被认为是导致特殊焦虑症的原因之一。本研究的目的是评估饮食中n-3和n-6多不饱和脂肪酸比例(3：6)是否影响恐惧记忆。为此，采用情境恐惧条件反射的方法研究了不同饮食比例3：6对小鼠恐惧记忆的影响，并考察了这些饮食对中枢突触传递的影响，以阐明多不饱和脂肪酸的作用机制。我们发现小鼠的恐惧记忆与饮食、血清和大脑的比例为3：6呈负相关。大麻素CB1受体拮抗剂利莫那班增加了高3：6饮食小鼠的低恐惧记忆，达到了低3：6饮食小鼠的水平。与低3：6饲料喂养的小鼠相比，高3：6饲料喂养的小鼠杏仁核基底外侧核(BLA)的CB1受体激动剂敏感性增强。通过药物清除脑片神经细胞膜中的胆固醇，在喂食低3：6比例饮食的小鼠中也产生了类似的增强作用。Cb1受体介导的短时突触可塑性在喂饲高3：6比例饲料的小鼠大脑皮质锥体神经元中得到促进。这些结果表明，n-3/n-6多不饱和脂肪酸的比例是通过大麻素CB1受体调节恐惧记忆的一个因素。
Although the underlying mechanism remains unknown, several studies have suggested benefits of n-3 long-chain polyunsaturated fatty acid (PUFA) for patients with anxiety disorders. Elevated fear is thought to contribute to the pathogenesis of particular anxiety disorders. The aim of the present study was to evaluate whether the dietary n-3 to n-6 PUFA (3: 6) ratio influences fear memory. For this purpose, the effects of various dietary 3: 6 ratios on fear memory were examined in mice using contextual fear conditioning, and the effects of these diets on central synaptic transmission were examined to elucidate the mechanism of action of PUFA. We found that fear memory correlated negatively with dietary, serum, and brain 3: 6 ratios in mice. The low fear memory in mice fed a high 3: 6 ratio diet was increased by the cannabinoid CB 1 receptor antagonist rimonabant, reaching a level seen in mice fed a low 3: 6 ratio diet. The agonist sensitivity of CB 1 receptor was enhanced in the basolateral nucleus of the amygdala (BLA) of mice fed a high 3: 6 ratio diet, compared with that of mice fed a low 3: 6 ratio diet. Similar enhancement was induced by pharmacological expulsion of cholesterol in the neuronal membrane of brain slices from mice fed a low 3: 6 ratio diet. CB 1 receptor-mediated short-term synaptic plasticity was facilitated in pyramidal neurons of the BLA in mice fed a high 3: 6 ratio diet. These results suggest that the ratio of n-3 to n-6 PUFA is a factor regulating fear memory via cannabinoid CB 1 receptors.