Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, PR China.
College of Pharmacy, Western University of Health Science, 309 East 2nd Street, Pomona, CA, 91766, USA.
Brain Res Bull. 2021 Jul;172:61-78. doi: 10.1016/j.brainresbull.2021.04.010. Epub 2021 Apr 20.
Although the global incidence of neurodegenerative diseases has been steadily increasing, especially in adults, there are no effective therapeutic interventions. Neurodegeneration is a heterogeneous group of disorders that is characterized by the activation of immune cells in the central nervous system (CNS) (e.g., mast cells and microglia) and subsequent neuroinflammation. Mast cells are found in the brain and the gastrointestinal tract and play a role in "tuning" neuroimmune responses. The complex bidirectional communication between mast cells and gut microbiota coordinates various dynamic neuro-cellular responses, which propagates neuronal impulses from the gastrointestinal tract into the CNS. Numerous inflammatory mediators from degranulated mast cells alter intestinal gut permeability and disrupt blood-brain barrier, which results in the promotion of neuroinflammatory processes leading to neurological disorders, thereby offsetting the balance in immune-surveillance. Emerging evidence supports the hypothesis that gut-microbiota exert a pivotal role in inflammatory signaling through the activation of immune and inflammatory cells. Communication between inflammatory cytokines and neurocircuits via the gut-brain axis (GBA) affects behavioral responses, activates mast cells and microglia that causes neuroinflammation, which is associated with neurological diseases. In this comprehensive review, we focus on what is currently known about mast cells and the gut-brain axis relationship, and how this relationship is connected to neurodegenerative diseases. We hope that further elucidating the bidirectional communication between mast cells and the GBA will not only stimulate future research on neurodegenerative diseases but will also identify new opportunities for therapeutic interventions.
尽管神经退行性疾病的全球发病率一直在稳步上升,尤其是在成年人中,但目前尚无有效的治疗干预措施。神经退行性变是一组异质性疾病,其特征是中枢神经系统(CNS)中免疫细胞的激活(例如,肥大细胞和小胶质细胞)和随后的神经炎症。肥大细胞存在于大脑和胃肠道中,在“调整”神经免疫反应中发挥作用。肥大细胞和肠道微生物群之间复杂的双向通讯协调各种动态神经细胞反应,将来自胃肠道的神经元冲动传播到中枢神经系统。脱颗粒肥大细胞中的许多炎症介质改变肠道通透性并破坏血脑屏障,导致神经炎症过程的促进,从而导致神经紊乱,从而抵消免疫监视的平衡。新出现的证据支持这样一种假设,即肠道微生物群通过激活免疫和炎症细胞在炎症信号中发挥关键作用。通过肠道-大脑轴(GBA)的炎症细胞因子和神经回路之间的通讯会影响行为反应,激活肥大细胞和小胶质细胞,导致神经炎症,这与神经退行性疾病有关。在这篇综合综述中,我们重点介绍了目前已知的肥大细胞和肠道-大脑轴关系,以及这种关系如何与神经退行性疾病相关。我们希望进一步阐明肥大细胞与 GBA 之间的双向通讯不仅将激发对神经退行性疾病的未来研究,而且还将为治疗干预提供新的机会。