Freeze-Dried Blueberries: Prevention and Rehabilitation Strategies in MS

冻干蓝莓：多发性硬化症的预防和康复策略

• 批准号: 8003795
• 负责人: SUSAN O MCGUIRE
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003795
• 关键词: Address; Adjuvant; Adverse effects; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Astrocytes; Behavior; Blueberries; Botanicals; Caring; Chronic; Clinical; Cognition; Complementary and alternative medicine; Development; Diet; Diet therapy; Dietary Supplementation; Disease; Dose; Effector Cell; Experimental Autoimmune Encephalomyelitis; Fatigue; Flavonoids; Freeze Drying; Healthcare; Heat-Shock Response; Human; Human Characteristics; Immune; Immune response; Immunosuppression; Impaired cognition; Incidence; Inflammation; Inflammatory; Intervention; Mediating; Mental Depression; Microglia; Mission; Modeling; Motor; Multiple Sclerosis; Mus; Neurologic; Patient Care; Patients; Pharmaceutical Preparations; Powder dose form; Prevention strategy; Preventive; Production; Property; Quality of life; Relapse; Reporting; Research Design; Respondent; Services; Severities; Signal Transduction; Supplementation; Symptoms; System; T cell response; T-Lymphocyte; Testing; Therapeutic; Veterans; cognitive function; cost; cytokine; daily functioning; depressive symptoms; design; dietary supplements; disability; feeding; immune function; improved; mouse model; neuroinflammation; neuroprotection; novel; prevent; prospective; protective effect; rehabilitation strategy; response; treatment strategy

DESCRIPTION (provided by applicant): Diet therapy may provide a low cost alternative and/or adjuvant treatment to improve the care of veterans suffering from service-connected Multiple Sclerosis (MS). Botanicals are protective in MS animal models by modulating immune function and decreasing inflammation. Some also improve cognition and depression in animals, symptoms that are troublesome for the MS patient. Blueberries, in particular, can alter immune function, decrease inflammation and alter expression of proinflammatory cytokines, thought to be responsible for some of the sickness behavior, such as depression, fatigue and cognitive dysfunction, in MS. We have shown that dietary supplementation with whole, freeze-dried blueberry powder (WBBP) decreased by greater than 50%, the incidence of symptoms in a mouse model of MS and significantly improved symptoms in blueberry-fed mice that did get sick. We hypothesize that blueberry powder will have a dose-dependent effect in both preventing and ameliorating clinical and depressive symptoms in EAE mice. The following specific aims will be used to test this hypothesis: This proposal is designed to establish the therapeutic potential of blueberries as a prospective supplement to reduce the severity of symptoms in MS patients. This will be accomplished by testing whole blueberry powder in several different models of EAE to represent the heterogeneous nature of human MS. Further, we will determine whether the mechanism(s) of previously described blueberry protection involves alteration of immune cell effector function. Specifically, we will test the following hypothesis: blueberry supplementation shifts EAE immune response from a Th1 to a Th2 response with subsequent decrease in neuroinflammation. This hypothesis will be tested in three specific aims: Specific Aim 1: Determine whether blueberry protection in chronic EAE is a result of altered immune cell effector function. This aim will determine whether blueberry protection is a result of a shift from Th1 to Th2 T cell profiles including altered cytokine production. Specific Aim 2: Determine whether blueberry is protective in relapsing-remitting EAE. This aim will allow us to test the potential preventive and ameliorative properties of blueberry supplementation. Specific Aim 3: Determine whether blueberry protective effects are due to alterations in the NFkB:IkB signaling system. NFkB activation mediates inflammatory activation in microglia and astrocytes; this aim will allow us to determine NFkB involvement in blueberry neuroprotection. In summary, these studies are designed to determine whether there is potential for blueberries to be used as a supplement to reduce the severity of MS in humans. It is highly significant because of the lack of adequate current strategies to improve the quality of life for MS patients. Development of this novel diet therapy may provide significant direct and/or synergistic benefits in the treatment of MS at low cost with few side effects. These studies are of particular significance to potential treatment of MS since even the best pharmacological interventions have significant side effect and may interact with multiple other MS medications. However, diet therapy is easily administered, well tolerated and has few side effects. PUBLIC HEALTH RELEVANCE: Approximately 20,000 MS patients were cared for by the VA in 2002 (Vollmer et al., 2002) at a cost of more than $2.2 million dollars over patient's lifetime (Whetten-Goldstein et al., 1998). However, these therapies are only partially effective (Lo et al, 2005) and do not address MS-associated cognitive dysfunction, fatigue and depression which cause significant disability and lessen quality of life (Bagert et al., 2002; Crayton and Rossman, 2006; Deloire et al., 2006; McCrone et al., 2008). Treatment strategies that improve these parameters as well as improve motor function would be greatly useful in helping MS patients maintain life quality (Hadjimichael et al., 2008) particularly if the strategy was without pharmacologic side effects and medication interactions. Diet therapy offers an inexpensive, easily administered, and well tolerated strategy with few side effects or medication interactions. It may improve or maintain daily function and quality of life in MS patients as well as improve motor function, factors of critical importance to the VA Patient Care Mission.

描述（由申请人提供）： 饮食疗法可以提供低成本的替代和/或辅助治疗，以改善患有与服务相关的多发性硬化症（MS）的退伍军人的护理。植物药通过调节免疫功能和减少炎症在MS动物模型中具有保护作用。有些还可以改善动物的认知和抑郁，这些症状对MS患者来说是麻烦的。特别是蓝莓，可以改变免疫功能，减少炎症和改变促炎细胞因子的表达，这些细胞因子被认为是MS中一些疾病行为的原因，如抑郁症，疲劳和认知功能障碍。我们已经证明，膳食补充完整的冻干蓝莓粉（WBBP）减少了50%以上，在MS小鼠模型中症状的发生率，以及在确实患病的蓝莓喂养小鼠中症状的显著改善。我们假设蓝莓粉在预防和改善EAE小鼠的临床和抑郁症状方面具有剂量依赖性作用。以下具体目标将用于测试这一假设：该提案旨在确定蓝莓作为一种前瞻性补充剂的治疗潜力，以降低MS患者症状的严重程度。这将通过在几种不同的EAE模型中测试整个蓝莓粉来实现，以代表人类MS的异质性。此外，我们将确定先前描述的蓝莓保护机制是否涉及免疫细胞效应子功能的改变。具体来说，我们将测试以下假设：蓝莓补充剂将EAE免疫反应从Th 1转变为Th 2反应，随后减少神经炎症。具体目标1：确定蓝莓对慢性EAE的保护作用是否是免疫细胞效应功能改变的结果。这一目标将确定蓝莓保护是否是从Th 1 T细胞向Th 2 T细胞转变的结果，包括改变细胞因子的产生。具体目标2：确定蓝莓是否在复发缓解型EAE中具有保护作用。这一目标将使我们能够测试蓝莓补充剂的潜在预防和改善特性。具体目标3：确定蓝莓的保护作用是否是由于NFkB：IkB信号系统的改变。NFkB激活介导小胶质细胞和星形胶质细胞的炎症激活;这一目的将使我们能够确定NFkB参与蓝莓神经保护。总之，这些研究旨在确定蓝莓是否有可能作为一种补充剂来降低人类MS的严重程度。这是非常重要的，因为缺乏足够的当前策略，以提高MS患者的生活质量。这种新型饮食疗法的开发可能会以低成本、少副作用的方式为MS的治疗提供显着的直接和/或协同益处。这些研究对MS的潜在治疗具有特别重要的意义，因为即使是最好的药物干预也具有显著的副作用，并且可能与多种其他MS药物相互作用。然而，饮食疗法易于管理，耐受性好，副作用少。 公共卫生相关性： 在2002年，大约20，000名MS患者由VA护理（Vollmer等人，2002），在患者的一生中花费超过220万美元（Whetten-Goldstein等人，1998年）。然而，这些疗法仅部分有效（Lo等，2005），并且不能解决MS相关的认知功能障碍、疲劳和抑郁，其导致显著的残疾和降低生活质量（Bagert等，2002年; Crayton和Rossman，2006年; Deloire等人，2006; McCrone等人，2008年）。改善这些参数以及改善运动功能的治疗策略将在帮助MS患者维持生活质量方面非常有用（Hadjimichael等人，2008），特别是如果该策略没有药理学副作用和药物相互作用。饮食疗法提供了一种廉价，易于管理，耐受性良好的策略，副作用或药物相互作用很少。它可以改善或维持MS患者的日常功能和生活质量，以及改善运动功能，这是VA患者护理使命的关键重要因素。