A mixed polyunsaturated fatty acid diet normalizes hippocampal neurogenesis and reduces anxiety in serotonin transporter knockout rats
A mixed polyunsaturated fatty acid diet normalizes hippocampal neurogenesis and reduces anxiety in serotonin transporter knockout rats
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DOI：
10.1097/fbp.0b013e328347881b
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发表时间：
2011-08-01
影响因子：
1.6
通讯作者：
Homberg, Judith R.
中科院分区：
文献类型：
--
作者：
Schipper, Pieter;Kiliaan, Amanda J.;Homberg, Judith R.
本研究的目的是研究混合饮食干预对5-羟色胺转运体敲除（5-HTT-/-）大鼠行为症状的影响，这些大鼠模拟了人类5-HTT长度多态性区短等位基因。将20只雌性5-HTT-/-和19只野生型（5-HTT+/+）大鼠喂食3个月的混合多不饱和脂肪酸（PUFA）饮食，包括n-3 PUFA、B族维生素和磷脂，或等热量控制饮食，然后对一个亚组进行一系列焦虑相关行为测试。所有的大脑都被采集并进行双皮质素免疫染色，双皮质素是一种神经发生标志物。此外，测量海马体积。控制饮食的5-HTT-/-大鼠表现出焦虑相关的行为反应增加，恐惧消退受损。这些影响被混合PUFA饮食完全抵消，而这种饮食对5-HTT+/+大鼠没有行为影响。与此同时，饲喂对照饲料的5-HTT-/-大鼠齿状回双皮质素免疫反应性增加，而饲喂混合PUFA饲料的大鼠则相反。5-HTT-/-受试者的海马体积不受混合PUFA饮食的影响，而5-HTT+/+大鼠的海马体积增加。我们得出结论，混合n-3 PUFA饮食以基因型依赖的方式改善焦虑相关症状，可能通过使神经发生正常化。我们认为，这种混合饮食可能作为一种有吸引力的辅助治疗焦虑的5-HTT长度多态性区域短等位基因携带者。行为药理学22:324-334 (C) 2011 Wolters Kluwer Health垂直bar Lippincott Williams & Wilkins。
The aim of this study was to investigate the effects of a mixed dietary intervention on behavioral symptoms in serotonin transporter knockout (5-HTT-/-) rats modeling the human 5-HTT length polymorphic region short-allele. Twenty female 5-HTT-/- and 19 wild-type (5-HTT+/+) rats were fed for 3 months on a mixed polyunsaturated fatty acid (PUFA) diet comprising n-3 PUFAs, B vitamins and phospholipids, or an isocaloric control diet, and a subgroup was subsequently tested in an array of anxiety-related behavioral tests. All brains were harvested and immunostained for doublecortin, a neurogenesis marker. In addition, hippocampal volume was measured. 5-HTT-/- rats on the control diet displayed increased anxiety-related behavioral responses, and impaired fear extinction. These effects were completely offset by the mixed PUFA diet, whereas this diet had no behavioral effect in 5-HTT+/+ rats. In parallel, dentate gyrus doublecortin immunoreactivity was increased in 5-HTT-/- rats fed on the control diet, which was reversed by the mixed PUFA diet. Hippocampal volume was unaffected by the mixed PUFA diet in 5-HTT-/- subjects, whereas it increased in 5-HTT+/+ rats. We conclude that a mixed n-3 PUFA diet ameliorates anxiety-related symptoms in a genotype-dependent manner, potentially by normalizing neurogenesis. We suggest that such a mixed diet may serve as an attractive adjuvant to treat anxiety in 5-HTT length polymorphic region short-allele carriers. Behavioural Pharmacology 22:324-334 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.