Kafami Laya, Raza Mohsin, Razavi Alireza, Mirshafiey Abbas, Movahedian Mansooreh, Khorramizadeh Mohammad Reza
Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Avicenna J Med Biotechnol. 2010 Jan;2(1):47-52.
Multiple Sclerosis (MS) is an autoimmune inflammatory, demyelinating disease of human central nervous system. Experimental Autoimmune Encephalomyelitis (EAE) is the commonly used animal model of MS. Calorie restriction has been found to reduce inflammation and autoimmune responses and promote neuroprotection. In this study we evaluated the effects of intermittent feeding protocol of the calorie restriction in a mouse model of EAE. Fifty four female mice (C57BL/6) were used in this study. The animals were divided into two dietary groups: ad libitum (AL) (n = 29) with free access to food and water and intermittent feeding (IF) (n = 25) with access to food on alternate days. After 8 weeks, EAE was induced in animals by immunization with MOG antigen (Hooke labs, Lawrence, MA, USA) subcutaneously. AL and IF groups were then further divided into two groups each: AA (ad libitum until the end of study) (n = 16) and AI (subjected to intermittent feeding regimen after immunization day) (n = 13). The IF group was divided into II (continued intermittent feeding regimen until the end of study) (n = 13) and IA (changed to AL regimen after immunization day) (n = 12). All the animals were behaviorally monitored for 35 days after immunization and observed daily for the signs and severity of disease with EAE scoring scale [0-5] and cumulative disease index (CDI) score. Intermittent feeding significantly reduced the incidence of EAE in IF groups (AI 0%, II 18.5%, IA 22.2%, p < 0.05). In addition, intermittent feeding significantly delayed the onset of EAE in AI group (p < 0.05) and also, intermittent feeding significantly reduced the severity of disease in II and IA groups (AA vs. II, p < 0.05 & AA vs. IA p < 0.05) groups. The CDI was also significantly reduced in intermittent feeding fed groups [AI, II and IA compared to AA group (P < 0.05, <0.01, <0.05 respectively)]. Intermittent feeding regimen protocol of the calorie restriction significantly suppressed EAE incidence, induction, and severity. The results of this study suggest possible role of intermittent feeding in the treatment of Multiple Sclerosis patients.
多发性硬化症（MS）是一种人类中枢神经系统的自身免疫性炎症性脱髓鞘疾病。实验性自身免疫性脑脊髓炎（EAE）是常用的MS动物模型。已发现热量限制可减轻炎症和自身免疫反应，并促进神经保护。在本研究中，我们评估了热量限制的间歇性喂养方案在EAE小鼠模型中的作用。本研究使用了54只雌性小鼠（C57BL/6）。将动物分为两个饮食组：自由进食（AL）组（n = 29），可自由获取食物和水；间歇性喂养（IF）组（n = 25），每隔一天进食一次。8周后，通过皮下注射MOG抗原（美国马萨诸塞州劳伦斯市胡克实验室）诱导动物发生EAE。然后将AL组和IF组进一步各自分为两组：AA组（自由进食直至研究结束）（n = 16）和AI组（免疫接种日后接受间歇性喂养方案）（n = 13）。IF组分为II组（持续间歇性喂养方案直至研究结束）（n = 13）和IA组（免疫接种日后改为自由进食方案）（n = 12）。免疫接种后对所有动物进行35天的行为监测，并每天观察疾病的体征和严重程度，使用EAE评分量表[0 - 5]和累积疾病指数（CDI）评分。间歇性喂养显著降低了IF组中EAE的发病率（AI组0%，II组18.5%，IA组22.2%，p < 0.05）。此外，间歇性喂养显著延迟了AI组中EAE的发病（p < 0.05），并且间歇性喂养显著降低了II组和IA组中疾病的严重程度（AA组与II组相比，p < 0.05；AA组与IA组相比，p < 0.05）。与AA组相比，间歇性喂养组的CDI也显著降低[AI组、II组和IA组分别为（P < 0.05、<0.01、<0.05）]。热量限制的间歇性喂养方案显著抑制了EAE的发病率、诱导和严重程度。本研究结果表明间歇性喂养在治疗多发性硬化症患者中可能发挥作用。
