Freeze-Dried Blueberries: Prevention and Rehabilitation Strategies in MS

描述(由申请人提供)： 饮食疗法可能提供一种低成本的替代和/或辅助治疗，以改善患有服务相关性多发性硬化症(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，在多发性硬化动物模型中具有保护作用。一些还可以改善动物的认知和抑郁，这些症状对多发性硬化症患者来说是很麻烦的。尤其是蓝莓，可以改变免疫功能，减少炎症，改变促炎细胞因子的表达，这些细胞因子被认为是导致MS的一些疾病行为的原因，如抑郁、疲劳和认知功能障碍。我们已经证明，在饮食中补充完整的冷冻干燥蓝莓粉(WBBP)可以降低50%以上，减少MS小鼠模型中的症状发生率，并显著改善确实患病的蓝莓喂养小鼠的症状。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的效应。以下具体目标将用于验证这一假设：这项提议旨在建立蓝莓作为一种预期的补充以减轻多发性硬化症患者症状的治疗潜力。这将通过在几种不同的EAE模型中测试整个蓝莓粉末来代表人类多发性硬化症的异质性来实现。此外，我们将确定先前描述的蓝莓保护机制(S)是否涉及免疫细胞效应器功能的改变。具体地说，我们将测试以下假设：蓝莓补充剂将EAE免疫反应从Th1反应转变为Th2反应，并随后减少神经炎症。这一假设将在三个具体目标中得到检验：具体目标1：确定慢性EAE中蓝莓的保护是否是免疫细胞效应器功能改变的结果。这一目标将决定蓝莓的保护是否是从Th1向Th2 T细胞类型转变的结果，包括细胞因子产生的改变。具体目标2：确定蓝莓对复发缓解的EAE是否具有保护作用。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性能。具体目标3：确定蓝莓的保护作用是否源于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。总而言之，这些研究旨在确定蓝莓是否有可能被用作补充，以降低人类多发性硬化症的严重程度。这是非常有意义的，因为目前缺乏足够的策略来改善MS患者的生活质量。这种新的饮食疗法的开发可能在治疗多发性硬化症方面提供显著的直接和/或协同效益，成本低，副作用少。这些研究对多发性硬化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有显著的副作用，并可能与多种其他多发性硬化症药物相互作用。然而，饮食疗法易于管理，耐受性好，几乎没有副作用。

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.