Department of Neurology, University Hospital Regensburg, Regensburg, Germany.
Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Front Immunol. 2024 Aug 9;15:1367819. doi: 10.3389/fimmu.2024.1367819. eCollection 2024.
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.
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 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).
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 analysis revealed an increased apoptosis of oligodendrocytes isolated from mice adapted on a galactose-rich diet. , treatment of cells with galactose neither impaired the maturation nor survival of oligodendroglial cells or iPNs. However, incubation of proteins with galactose 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.
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.
最近的研究为生活方式因素（包括饮食）在神经炎症性疾病（如多发性硬化症（MS））发病机制中的重要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通过增强炎症但减弱调节免疫过程使疾病恶化，而作为我们日常饮食中另一个突出成分的糖迄今为止仅被很少研究。除葡萄糖和果糖外，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，研究神经炎症期间富含半乳糖饮食的影响。我们通过流式细胞术分析研究外周免疫反应和炎症浸润，并对脊髓进行组织学染色，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晚期糖基化终产物（AGEs）的形成，并研究寡突胶质细胞培养物和诱导多能干细胞衍生的原代神经元（iPNs）中的半乳糖和半乳糖诱导的 AGEs。
喂食富含半乳糖饮食的年轻小鼠在 EAE 的急性期表现出更严重的疾病症状，在慢性期恢复受损。半乳糖不影响外周免疫反应或炎症浸润到 CNS，但导致脱髓鞘、少突胶质细胞丢失和增强神经轴突损伤分析显示，从适应富含半乳糖饮食的小鼠中分离的少突胶质细胞凋亡增加。此外，用半乳糖处理细胞既不会损害少突胶质细胞或 iPNs 的成熟或存活。然而，半乳糖孵育蛋白会导致 AGEs 的形成，在喂食富含半乳糖饮食的 EAE 患病小鼠的脊髓中增加。在寡突胶质细胞和神经元培养物中，与对照处理相比，用半乳糖处理诱导 AGEs 可促进细胞死亡增加。
这些结果表明，神经炎症期间半乳糖诱导的少突胶质细胞和髓鞘损伤可能是通过 AGEs 介导的，从而将半乳糖及其反应产物鉴定为多发性硬化症等神经炎症性疾病的潜在饮食风险因素。
