■最近的研究为包括饮食在内的生活方式因素在多发性硬化症(MS)等神经炎性疾病的发病机理中的相关作用提供了越来越多的证据。在MS的实验模型中,饱和脂肪酸和盐的摄入会通过增强的炎症但减少的调节免疫过程来恶化疾病结果。到目前为止,糖作为我们日常饮食中的其他重要成分几乎没有被研究过。除了葡萄糖和果糖,半乳糖是所谓的西方饮食中的常见糖。
我们使用髓鞘少突胶质细胞糖蛋白诱导的实验性自身免疫性脑脊髓炎(MOG-EAE)作为模型疾病,研究了富含半乳糖的饮食在神经炎症期间的作用。我们通过离体流式细胞术分析研究了外周免疫反应和炎症浸润,并对脊髓进行了组织学染色,以分析半乳糖在中枢神经系统(CNS)中的作用。我们通过荧光测量分析了晚期糖基化终产物(AGEs)的形成,并研究了少突胶质细胞培养物中的半乳糖以及半乳糖诱导的AGEs和诱导的多能干细胞衍生的原代神经元(iPNs)。
饲喂富含半乳糖的饮食的年轻小鼠在EAE的急性期表现出加重的疾病症状以及在慢性期的受损恢复。半乳糖不影响外周免疫反应或炎症浸润到中枢神经系统,但导致脱髓鞘增加,少突胶质细胞损失和增强的神经轴突损伤。离体分析显示,从适应富含半乳糖饮食的小鼠中分离出的少突胶质细胞的凋亡增加。体外,用半乳糖处理细胞不会损害少突胶质细胞或iPN的成熟或存活。然而,在体外培养蛋白质与半乳糖导致形成AGEs,在喂食富含半乳糖的饮食的EAE患病小鼠的脊髓中增加。在少突胶质细胞和神经元培养中,与对照处理相比,用半乳糖诱导的AGEs处理促进增强的细胞死亡。
■这些结果表明,神经炎症过程中半乳糖诱导的少突胶质细胞和髓鞘损伤可能是由AGEs介导的,从而确定半乳糖及其反应产物是神经炎性疾病如MS的潜在饮食危险因素。
UNASSIGNED: Recent studies provide increasing evidence for a relevant role of lifestyle factors including diet in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). While the intake of saturated fatty acids and elevated salt worsen the disease outcome in the experimental model of MS by enhanced inflammatory but diminished regulatory immunological processes, sugars as additional prominent components in our daily diet have only scarcely been investigated so far. Apart from glucose and fructose,
galactose is a common sugar in the so-called Western diet.
UNASSIGNED: We investigated the effect of a
galactose-rich diet during neuroinflammation using myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE) as a model disease. We investigated peripheral immune reactions and inflammatory infiltration by ex vivo flow cytometry analysis and performed histological staining of the spinal cord to analyze effects of galactose in the central nervous system (CNS). We analyzed the formation of advanced glycation end products (AGEs) by fluorescence measurements and investigated galactose as well as galactose-induced AGEs in oligodendroglial cell cultures and induced pluripotent stem cell-derived primary neurons (iPNs).
UNASSIGNED: Young mice fed a
galactose-rich diet displayed exacerbated disease symptoms in the acute phase of EAE as well as impaired recovery in the chronic phase. Galactose did not affect peripheral immune reactions or inflammatory infiltration into the CNS, but resulted in increased demyelination, oligodendrocyte loss and enhanced neuro-axonal damage. Ex vivo analysis revealed an increased apoptosis of oligodendrocytes isolated from mice adapted on a galactose-rich diet. In vitro, treatment of cells with galactose neither impaired the maturation nor survival of oligodendroglial cells or iPNs. However, incubation of proteins with
galactose in vitro led to the formation AGEs, that were increased in the spinal cord of EAE-diseased mice fed a
galactose-rich diet. In oligodendroglial and neuronal cultures, treatment with galactose-induced AGEs promoted enhanced cell death compared to control treatment.
UNASSIGNED: These results imply that galactose-induced oligodendrocyte and myelin damage during neuroinflammation may be mediated by AGEs, thereby identifying galactose and its reactive products as potential dietary risk factors for neuroinflammatory diseases such as MS.