Van Gaever Femke, Mingneau Fleur, Vanherle Sam, Driege Yasmine, Haegman Mira, Van Wonterghem Elien, Xie Junhua, Vandenbroucke Roosmarijn E, Hendriks Jerome J A, Beyaert Rudi, Staal Jens
VIB-UGent Center for Inflammation Research, VIB, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Front Immunol. 2024 Dec 17;15:1500697. doi: 10.3389/fimmu.2024.1500697. eCollection 2024.
Over the past few decades, there has been a sudden rise in the incidence of Multiple Sclerosis (MS) in Western countries. However, current treatments often show limited efficacy in certain patients and are associated with adverse effects, which highlights the need for safer and more effective therapeutic approaches. Environmental factors, particularly dietary habits, have been observed to play a substantial role in the development of MS. In this study, we are the first to investigate the potential protective effect of the phytohormone abscisic acid (ABA) in MS. ABA, which is abundant in fruits such as figs, apricots and bilberries, is known to cross the blood-brain barrier and has demonstrated neuroprotective effects in conditions like depression and Alzheimer's disease.
In this study, we investigated whether ABA supplementation enhances remyelination in both and mouse models.
Our results indicated that ABA enhanced remyelination and that this enhanced remyelination is associated with increased lipid droplet load, reduced levels of degraded myelin, and a higher abundance of F4/80+ cells in the demyelinated brain of mice treated with ABA. In models, we further demonstrated that ABA treatment elevates lipid droplet formation by enhancing the phagocytic capacity of macrophages. Additionally, in a mouse model of microglial activation, we showed that ABA-treated mice maintain a less inflammatory microglial phenotype.
Our findings highlight a crucial role for macrophages and microglia in enabling ABA to enhance the remyelination process. Furthermore, ABA's ability to improve remyelination together with its ability to reduce microglial activation, make ABA a promising candidate for modulating macrophage phenotype and reducing neuroinflammation in MS.
在过去几十年中,西方国家多发性硬化症(MS)的发病率突然上升。然而,目前的治疗方法在某些患者中往往疗效有限,且伴有不良反应,这凸显了对更安全、更有效治疗方法的需求。已观察到环境因素,特别是饮食习惯,在MS的发展中起着重要作用。在本研究中,我们首次调查了植物激素脱落酸(ABA)在MS中的潜在保护作用。ABA在无花果、杏子和越橘等水果中含量丰富,已知其可穿过血脑屏障,并在抑郁症和阿尔茨海默病等病症中表现出神经保护作用。
在本研究中,我们调查了补充ABA是否能增强EAE和LPC小鼠模型中的髓鞘再生。
我们的结果表明,ABA增强了髓鞘再生,并且这种增强的髓鞘再生与脂质滴负荷增加、降解髓鞘水平降低以及用ABA处理的小鼠脱髓鞘脑中F4/80+细胞丰度较高有关。在EAE模型中,我们进一步证明ABA处理通过增强巨噬细胞的吞噬能力提高了脂质滴的形成。此外,在小胶质细胞激活的小鼠模型中,我们表明用ABA处理的小鼠维持了炎症较轻的小胶质细胞表型。
我们的研究结果突出了巨噬细胞和小胶质细胞在使ABA增强髓鞘再生过程中的关键作用。此外,ABA改善髓鞘再生的能力及其降低小胶质细胞激活的能力,使ABA成为调节巨噬细胞表型和减轻MS中神经炎症的有希望的候选物。