背景:这篇叙述性综述探讨了压力相关疾病如抑郁症的临床挑战,专注于神经元特异性和细胞促炎机制之间的相互作用,大脑,和系统水平。
目的:我们旨在阐明慢性心理应激与关键脑区低度神经炎症的分子机制,特别关注G蛋白和5-羟色胺(5-HT)受体的作用。
方法:对文献的全面回顾采用了系统的,叙事,和范围审查方法,结合全身病理学方法。它综合了目前对参与应激反应和神经炎症的共享信号通路的研究,包括钙依赖性机制,丝裂原活化蛋白激酶,和关键转录因子如NF-κB和p53。该综述还着重于G蛋白偶联神经递质受体(GPCRs)在免疫和促炎反应中的作用。详细分析了14种人类5-HT受体中的13种如何导致抑郁症和神经炎症。
结果:该综述揭示了应激相关病理中神经递质信号与免疫炎症反应之间的复杂相互作用。它强调了GPCRs和典型炎症介质在影响神经组织的病理和生理过程中的作用。
结论:提出的神经免疫炎症应激模型(NIIS模型)表明促炎信号通路,由代谢型和离子型神经递质受体介导,对维持神经元稳态至关重要。慢性精神压力会破坏这种平衡,导致大脑中促炎状态增加,并导致神经精神和心身疾病,包括抑郁症。该模型整合了抑郁症发病机制的传统理论,全面了解病情的多面性。
This narrative
review addresses the clinical challenges in stress-related disorders such as depression, focusing on the interplay between neuron-specific and pro-inflammatory mechanisms at the cellular, cerebral, and systemic levels.
We aim to elucidate the molecular mechanisms linking chronic psychological stress with low-grade neuroinflammation in key brain regions, particularly focusing on the roles of G proteins and serotonin (5-HT) receptors.
This comprehensive
review of the literature employs systematic, narrative, and scoping
review methodologies, combined with systemic approaches to general pathology. It synthesizes current research on shared signaling pathways involved in stress responses and neuroinflammation, including calcium-dependent mechanisms, mitogen-activated protein kinases, and key transcription factors like NF-κB and p53. The
review also focuses on the role of G protein-coupled neurotransmitter receptors (GPCRs) in immune and pro-inflammatory responses, with a detailed analysis of how 13 of 14 types of human 5-HT receptors contribute to depression and neuroinflammation.
The
review reveals a complex interaction between neurotransmitter signals and immunoinflammatory responses in stress-related pathologies. It highlights the role of GPCRs and canonical inflammatory mediators in influencing both pathological and physiological processes in nervous tissue.
The proposed Neuroimmunoinflammatory Stress Model (NIIS Model) suggests that proinflammatory signaling pathways, mediated by metabotropic and ionotropic neurotransmitter receptors, are crucial for maintaining neuronal homeostasis. Chronic mental stress can disrupt this balance, leading to increased pro-inflammatory states in the brain and contributing to neuropsychiatric and psychosomatic disorders, including depression. This model integrates traditional theories on depression pathogenesis, offering a comprehensive understanding of the multifaceted nature of the condition.