Smirnova Maria I, Quan Ning
Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL, 33458, USA.
Stiles-Nicholson Brain Institute, Florida Atlantic University, Jupiter, FL, 33458, USA.
Neurobiol Sleep Circadian Rhythms. 2025 Apr 25;18(Suppl):100123. doi: 10.1016/j.nbscr.2025.100123. eCollection 2025 May.
Adult hippocampal neurogenesis (AHN) plays a critical role in cognition and emotional regulation. Recent studies have linked compromised AHN to numerous neurological and psychological disorders. The actions of the inflammatory cytokine interleukin-1 (IL-1) have been found to suppress AHN and antagonism of IL-1 signaling has been advocated as a therapeutic strategy for the treatment of neurodegenerative diseases and affective disorders. On the other hand, work from Jim Krueger's group revealed the physiological function of IL-1 in brain homeostasis, indicating the potential downside of IL-1 blockade. Current literature also shows AHN participates in normal functions of the brain in parallel to IL-1. This mini-review analyzes how IL-1 might positively or negatively modulate AHN and the implications of the relationship between IL-1 and AHN on health and disease. Specifically, we will highlight the parallels between IL-1 signaling and AHN in physiological and disease states. We propose that IL-1 signaling modulates AHN in a context-dependent manner; whereas its elevated signaling impairs neurogenesis and contributes to neurological and psychiatric disorders, its physiological role suggests potential therapeutic benefits of IL-1 antagonism must consider the preservation of the beneficial actions of IL-1.
成体海马神经发生(AHN)在认知和情绪调节中起着关键作用。最近的研究已将受损的AHN与多种神经和心理疾病联系起来。已发现炎性细胞因子白细胞介素-1(IL-1)的作用会抑制AHN,并且有人主张拮抗IL-1信号传导作为治疗神经退行性疾病和情感障碍的一种治疗策略。另一方面,吉姆·克鲁格团队的研究揭示了IL-1在脑内稳态中的生理功能,这表明了IL-1阻断存在潜在的不利方面。当前的文献还表明,AHN与IL-1并行参与大脑的正常功能。这篇小型综述分析了IL-1如何正向或负向调节AHN,以及IL-1与AHN之间的关系对健康和疾病的影响。具体而言,我们将强调生理和疾病状态下IL-1信号传导与AHN之间的相似之处。我们提出,IL-1信号传导以上下文依赖的方式调节AHN;虽然其信号传导升高会损害神经发生并导致神经和精神疾病,但其生理作用表明,IL-1拮抗作用的潜在治疗益处必须考虑保留IL-1的有益作用。