Schipper Pieter, Kiliaan Amanda J, Homberg Judith R
Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Behav Pharmacol. 2011 Aug;22(4):324-34. doi: 10.1097/FBP.0b013e328347881b.
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.
本研究旨在调查混合饮食干预对模拟人类5-羟色胺转运体（5-HTT）长度多态性区域短等位基因的5-羟色胺转运体基因敲除（5-HTT⁻/⁻）大鼠行为症状的影响。给20只雌性5-HTT⁻/⁻大鼠和19只野生型（5-HTT⁺/⁺）大鼠喂食包含n-3多不饱和脂肪酸（PUFA）、B族维生素和磷脂的混合多不饱和脂肪酸饮食或等热量对照饮食，为期3个月，随后对一个亚组进行一系列与焦虑相关的行为测试。采集所有大鼠的大脑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。食用对照饮食的5-HTT⁻/⁻大鼠表现出与焦虑相关的行为反应增加以及恐惧消退受损。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。同时，食用对照饮食的5-HTT⁻/⁻大鼠齿状回双皮质素免疫反应性增加，而混合PUFA饮食使其逆转。混合PUFA饮食对5-HTT⁻/⁻大鼠的海马体积没有影响，而在5-HTT⁺/⁺大鼠中则增加。我们得出结论，混合n-3 PUFA饮食以基因型依赖的方式改善与焦虑相关的症状，可能是通过使神经发生正常化。我们建议这种混合饮食可能作为一种有吸引力的辅助手段来治疗5-HTT长度多态性区域短等位基因携带者的焦虑症。
