外源L-糖减轻了由慢性不可预测的压力引起的抑郁症:涉及核心糖化,具有抗抑郁药的潜在作用
Dan Wang1, Tomohiko Fukuda2, Tiangui Wu1
1Division of Regulatory Glycobiology, Graduate School of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan.
The Journal of biological chemistry
|January 26, 2025
概括
在小鼠中,补充L-糖可减少类似抑郁症的行为和神经炎症. 这种核心的fucosylation修饰通过改善突触功能和减少炎症通路,显示出抗抑郁药的潜力.
科学领域:
- 生物化学和分子生物学
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
背景情况:
- 核化,一个由α1,6-fucosyltransferase (Fut8) 催化的关键N-甘氨酸修饰,在炎症反应中起作用.
- 神经炎症越来越被认为是抑郁症发展的关键因素.
- 之前的研究表明,Fut8淘汰赛小鼠在对脂聚糖化物 (LPS) 的反应中表现出高度的神经炎症.
研究的目的:
- 调查核心化在调节由慢性不可预测压力 (CUS) 引起的抑郁症中的作用.
- 在CUS诱导抑郁症的小鼠模型中评估L-糖的治疗潜力.
主要方法:
- 使用了Fut8异构结合的淘汰 (Fut8+/-) 和野生型 (Fut8+/+) 鼠标,这些鼠标遭受了慢性不可预测的压力 (CUS).
- 外源地给予L-糖,以评估其对类似抑郁的行为,神经炎症和突触标记物的影响.
- 分析了JAK2 / STAT3信号通路和gp130与互白素-6 (IL-6) 受体之间的相互作用.
主要成果:
- 与CUS下的Fut8+/-小鼠相比,Fut8+/-小鼠表现出更早出现抑郁类行为和增加的神经炎症.
- 在Fut8+/-小鼠中,L-糖的使用显著缓解了CUS诱导的抑郁行为,并降低了前炎性细胞因子水平.
- L-糖治疗减弱了gp130/IL-6受体复合体形成和JAK2/STAT3信号传递,增强了树突脊柱密度,增加了PSD-95表达.
结论:
- 核心化会影响CUS诱导的抑郁症和相关的神经炎症的发展.
- 通过改善神经炎症和突触缺陷,L-糖表现出显著的抗抑郁作用.
- L-糖显示出作为治疗抑郁症的治疗剂的潜力,准核心糖化通路.
相关概念视频
Long-term Depression
2.5K
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over...
Calcium Ion Concentration Mechanism
If over...
2.5K
Introduction to Stress and Lifestyle
73
Stress is a multifaceted response to events perceived as challenging or threatening, highlighting physical, emotional, cognitive, and behavioral reactions. Physically, stress can lead to fatigue, sleep disruptions, and various health issues such as frequent colds, chest pains, and nausea. Emotionally, it can manifest as anxiety, depression, irritability, and anger triggered by both minor and major life events. Cognitively, it may result in difficulty in concentration, memory, and...
73
Stress and Mental Health
71
Chronic stress profoundly affects mental health, significantly influencing mood, behavior, and overall quality of life. Research closely links chronic stress with mental health conditions such as depression, anxiety, and substance use disorders. Ongoing exposure to stress can lead to physiological and psychological changes, initiating a cycle of emotional distress and maladaptive coping mechanisms.
Individuals with depression often experience challenges in both their personal and professional...
Individuals with depression often experience challenges in both their personal and professional...
71


