Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis
Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis
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DOI：
10.1189/jlb.0208133
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发表时间：
2008-10-01
影响因子：
5.5
通讯作者：
Cross, Anne H.
中科院分区：
文献类型：
--
作者：
Piccio, Laura;Stark, Jennifer L.;Cross, Anne H.
热量限制（CR）可以预防许多与年龄相关的疾病并延长寿命。CR诱导多种代谢和生理改变，包括抗炎、抗氧化和神经保护作用，这些作用可能对多发性硬化症（MS）有益。本研究试图确定CR或增加的卡路里摄入是否改变实验性自身免疫性脑脊髓炎（EAE）（MS的主要动物模型）的过程。SJL和C57 BL/6小鼠从5周龄开始经受40%CR。CR 5周后，通过在SJL小鼠中用蛋白脂质蛋白免疫和在C57 BL/6小鼠中用髓鞘少突胶质细胞糖蛋白免疫诱导EAE。将EAE的临床、组织学和免疫学特征与自由进食的小鼠和高脂肪、高热量饮食的SJL小鼠进行比较。CR改善了两种小鼠品系的临床EAE，炎症、脱髓鞘和轴突损伤不太严重。未观察到免疫功能抑制。高热量饮食不会改变EAE的病程。CR与血浆皮质酮和脂联素水平升高以及IL-6和瘦素浓度降低相关。在我们的研究中观察到的CR诱导的激素，代谢和细胞因子的变化表明，联合抗炎和神经保护作用。应探索在充分营养和仔细的医学监测下的CR作为MS的潜在治疗方法。
Calorie restriction (CR) prevents many age-associated diseases and prolongs the lifespan. CR induces multiple metabolic and physiologic modifications, including anti-inflammatory, antioxidant, and neuroprotective effects that may be beneficial in multiple sclerosis (MS). The present studies sought to determine whether CR or increased calorie intake alters the course of experimental autoimmune encephalomyelitis (EAE), the leading animal model for MS. SJL and C57BL/6 mice were subjected to 40% CR beginning at 5 weeks of age. After 5 weeks of CR, EAE was induced by immunizing with proteolipid protein in SJL mice and with myelin oligodendrocyte glycoprotein in C57BL/6 mice. Clinical, histologic, and immunologic features of EAE were compared with mice fed ad libitum and to SJL mice fed a high-fat, high-calorie diet. CR ameliorated clinical EAE in both mouse strains with less severe inflammation, demyelination, and axon injury. No suppression of immune function was observed. A high-calorie diet did not alter the EAE course. CR was associated with increased plasma levels of corticosterone and adiponectin and reduced concentrations of IL-6 and leptin. The CR-induced hormonal, metabolic, and cytokine changes observed in our studies suggest a combined anti-inflammatory and neuroprotective effect. CR with adequate nutrition and careful medical monitoring should be explored as a potential treatment for MS.