慢性压力对晚期阿尔茨海默病病理学的矛盾保护作用
Yoel Shor1, Reut Said2, Nina Fainstein3
1Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; The Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Institute for Research in Military Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Brain, behavior, and immunity
|December 20, 2025
概括
患有阿尔茨海默氏症 (AD) 的老鼠的慢性压力和抑郁症降低了神经毒性髓状细胞活性,可能保护神经退行. 这表明针对微质的阶段依赖性疗法对阿尔茨海默病的进展至关重要.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
背景情况:
- 阿尔茨海默氏病 (AD) 涉及粉样β (Aβ) 斑块,滑症和神经元损失.
- 中年抑郁症增加了AD风险;晚年抑郁症在AD患者中很常见,但其在病变发生中的作用尚不清楚.
- 中枢神经系统 (CNS) 髓质细胞,如微质细胞,从清除Aβ转变为晚期AD的神经毒性表型,加剧神经退行.
研究的目的:
- 在临床前AD模型中研究慢性压力对微质功能和神经退行症的影响.
- 确定压力是否影响中枢神经系统髓质细胞功能障碍和在已确定的AD病理中神经退行过程.
主要方法:
- 在晚期临床前AD阶段 (7个月大) 使用了5xFAD小鼠模型.
- 应用了为期六周的慢性轻度压力 (CMS) 范式来诱导抑郁行为.
- 通过转录组学,激活标志物和氧化功能评估中枢神经系统髓质细胞激活状态;通过组织学评估神经元和微质密度.
主要成果:
- 非压力5xFAD小鼠显示过激活的髓状细胞状态.
- CMS抑制了免疫和代谢途径,减少了CD68的表达,并降低了中枢神经系统骨髓细胞中的氧化功能.
- 在关键的大脑区域中,CMS并没有诱导神经退行,并且保护免受微质介导的神经退行.
结论:
- 慢性压力和抑郁减弱中枢神经系统的髓状细胞.
- 这种减弱可能会阻止在已建立的AD中过渡到完全神经毒性微质,从而干扰神经退行.
- 针对微质细胞的疗法应考虑它们在阿尔茨海默病进展中的阶段性作用.
相关概念视频
Psychoneuroimmunology: Diabetes and Cancer
409
Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
409
Alzheimer's Disease: Overview
1.6K
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
1.6K
Aging
566
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
566
Stress and Mental Health
564
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...
564
Psychoneuroimmunology: Cardiovascular Disease
367
Psychoneuroimmunology (PNI) is a multidisciplinary field that examines how psychological factors, particularly stress, interact with the immune system and impact physical health. Research in PNI has shown that chronic or traumatic stress can disrupt both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. These disruptions contribute to serious health conditions, including cardiovascular diseases.
A key area of focus in PNI is the relationship between stress and coronary...
A key area of focus in PNI is the relationship between stress and coronary...
367
Alzheimer's Disease: Treatment
752
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
752


