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The impact of an omega-3 enriched diet on hyperactivity and biochemistry in an animal model of attentiondeficit/ hyperactivity disorder.

机译:注意缺陷多动障碍动物模型中富含欧米伽3的饮食对活动过度和生物化学的影响。

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摘要

Attention-deficit/hyperactivity disorder (ADHD) is the most diagnosed behavioral disorder in children. It affects around 5% of children worldwide and 11% of children in the United States, with rates increasing. Pharmaceutical treatments, such as amphetamines and methylphenidates, are not effective for everyone and are known to have unwanted side effects. While the etiology of the disorder is not yet fully understood, there are clear genetic and environmental components. Nutritional insufficiencies have recently become a popular environmental risk factor under investigation. Essential fatty acids (EFA), omega-3 polyunsaturated fatty acids (PUFA) in particular, are needed for proper brain development and function. Our lab has found lower proportions of omega-3 PUFA in the phospholipids and red blood cell membranes of about 40% of the children and adults with ADHD. Other research groups have subsequently confirmed similar findings. It is not yet known why a subgroup of the ADHD population seem to display EFA insufficiency, or if supplementation can reliably prevent or alleviate symptoms of the disorder. However, multiple human and animal studies have reported a reduction in ADHD-symptoms with omega-3 PUFA supplementation. Thus, we hypothesized that an omega-3 PUFA enriched diet would reduce the ADHD symptom of hyperactivity, modulate dopamine and serotonin turnover, and increase omega-3 PUFA proportion in plasma and brain phospholipids in the Spontaneously Hypertensive Rat (SHR) animal model for ADHD. Additionally, we explored the relationship between oxidative stress, EFA status, and ADHD behavior with the prediction that SHR will display greater oxidative stress than the control strain, Wistar Kyota Rat (WKY). In order to develop a protocol that elucidates the behavioral differences between the two rat strains, we conducted a pilot study on various behavioral tests on the WKY and SHR while on standard rat chow. Results from our preliminary data led us to use the open field test as a measure of hyperactivity. In our intervention study, the omega-3 enriched diet (omega-3 diet) had no impact on measures of hyperactivity. However, our intervention successfully increased omega-3 PUFA proportions in plasma and brain phospholipid membranes. WKY had a higher proportion of eicosapentaenoic acid (EPA) in both plasma and brain than SHR, and SHR had a higher proportion of docosahexaenoic acid in plasma for both diets. Results of the liver total glutathione (GSH) analysis suggested that the omega-3 diet reduced oxidative stress, but that the SHR had lower oxidative stress than the WKY. SHR on the omega-3 diet had a lower concentration of dopamine in the neostriatum than SHR on the omega-6 dominant diet, and both rat strains on the omega-3 diet had lower serotonin concentration. Consistent with the lack of impact on behavior, dopamine and serotonin turnover were not modulated by diet. However, dopamine turnover in the SHR was lower than that in the WKY. In summary, our dietary intervention did not impact behavior, which was consistent with the lack of impact on neurotransmission, despite the alteration in phospholipid proportions. Future studies should focus on determining the most effective dose, EPA/DHA ratio, and time period for an omega-3 PUFA intervention.
机译:注意缺陷/多动障碍(ADHD)是儿童中诊断最多的行为障碍。随着发病率的上升,它影响了全世界约5%的儿童和美国11%的儿童。诸如苯丙胺和哌醋甲酯之类的药物治疗并非对所有人都有效,并且已知具有不良副作用。尽管该病的病因尚未完全明了,但有明确的遗传和环境成分。营养不足最近已成为研究中流行的环境风险因素。必需脂肪酸(EFA),尤其是omega-3多不饱和脂肪酸(PUFA),对于大脑的正常发育和功能而言是必需的。我们的实验室发现,约40%患有ADHD的儿童和成人的磷脂和红细胞膜中的omega-3 PUFA比例较低。其他研究小组随后也证实了类似的发现。尚不清楚为什么ADHD人群的一个亚组似乎表现出EFA不足,或者补充是否可以可靠地预防或减轻该疾病的症状。然而,多项人类和动物研究报告称,补充omega-3 PUFA可以减轻ADHD症状。因此,我们假设富含omega-3 PUFA的饮食将减轻ADHD自发性高血压大鼠(SHR)动物模型中ADHD多动症的症状,调节多巴胺和血清素的转换并增加血浆和脑磷脂中omega-3 PUFA的比例。 。此外,我们探索了氧化应激,EFA状态和ADHD行为之间的关系,并预测SHR将显示出比对照菌株Wistar Kyota Rat(WKY)更大的氧化应激。为了开发一种协议,阐明两种大鼠品系之间的行为差​​异,我们对WKY和SHR在标准大鼠食物上的各种行为测试进行了初步研究。初步数据的结果使我们可以使用野外试验来测量多动。在我们的干预研究中,富含omega-3的饮食(omega-3饮食)对多动症的测量没有影响。但是,我们的干预成功地增加了血浆和脑磷脂膜中的omega-3 PUFA比例。与SHR相比,WKY在血浆和脑中的二十碳五烯酸(EPA)比例更高,并且两种饮食中SHR在血浆中的二十二碳六烯酸比例更高。肝脏总谷胱甘肽(GSH)分析结果表明,omega-3饮食降低了氧化应激,但SHR的氧化应激低于WKY。与以omega-6饮食为主的SHR相比,以omega-3饮食为主的SHR在新纹状体中的多巴胺浓度较低,并且以omega-3饮食为主的两种大鼠品系的血清素浓度均较低。与对行为没有影响一致,多巴胺和5-羟色胺的更新不受饮食调节。但是,SHR中的多巴胺周转率低于WKY中的多巴胺周转率。总之,尽管磷脂比例发生了变化,但我们的饮食干预并未影响行为,这与缺乏对神经传递的影响是一致的。未来的研究应侧重于确定omega-3 PUFA干预的最有效剂量,EPA / DHA比和时间段。

著录项

  • 作者

    Hammoud, Nadine M.;

  • 作者单位

    Purdue University.;

  • 授予单位 Purdue University.;
  • 学科 Nutrition.;Behavioral psychology.;Pharmacology.;Psychobiology.
  • 学位 M.S.
  • 年度 2014
  • 页码 98 p.
  • 总页数 98
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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