Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
J Alzheimers Dis. 2024;100(s1):S305-S325. doi: 10.3233/JAD-240635.
The September 11, 2001, catastrophe unleashed widespread destruction beyond the World Center (WTC), with fires and toxic gases leaving lasting impacts. First responders at Ground Zero faced prolonged exposure to hazardous particulate matter (PM), resulting in chronic health challenges. Among the multitude of health concerns, the potential association between the WTCPM and Alzheimer's disease (AD) has emerged as an area of intense inquiry, probing the intricate interplay between environmental factors and neurodegenerative diseases.
We posit that a genetic predisposition to AD in mice results in dysregulation of the gut-brain axis following chronic exposure to WTCPM. This, in turn, may heighten the risk of AD-like symptoms in these individuals.
3xTg-AD and WT mice were intranasally administered with WTCPM collected at Ground Zero within 72 hours after the attacks. Working memory and learning and recognition memory were monitored for 4 months. Moreover, brain transcriptomic analysis and gut barrier permeability along with microbiome composition were examined.
Our findings underscore the deleterious effects of WTCPM on cognitive function, as well as notable alterations in brain genes associated with synaptic plasticity, pro-survival, and inflammatory signaling pathways. Complementary, chronic exposure to the WTCPM led to increased gut permeability in AD mice and altered bacteria composition and expression of functional pathways in the gut.
Our results hint at a complex interplay between gut and brain axis, suggesting potential mechanisms through which WTCPM exposure may exacerbate cognitive decline. Identifying these pathways offers opportunities for tailored interventions to alleviate neurological effects among first responders.
2001 年 9 月 11 日的灾难不仅对世界贸易中心（WTC）造成了广泛破坏，还释放出的火灾和有毒气体造成了持久影响。“零地带”的急救人员长期暴露在危险的微粒物质（PM）中，导致他们面临慢性健康挑战。在众多健康问题中，WTC-PM 与阿尔茨海默病（AD）之间的潜在关联成为一个研究热点，探讨了环境因素与神经退行性疾病之间的复杂相互作用。
我们假设，AD 易感基因会导致慢性暴露于 WTCPM 后肠道-大脑轴的失调，从而增加这些个体出现 AD 样症状的风险。
3xTg-AD 和 WT 小鼠在攻击后 72 小时内通过鼻腔内给予 WTCPM 收集物。监测了 4 个月的工作记忆和学习及识别记忆。此外，还检查了大脑转录组分析、肠道屏障通透性以及微生物组组成。
我们的研究结果强调了 WTCPM 对认知功能的有害影响，以及与突触可塑性、生存促进和炎症信号通路相关的大脑基因的显著改变。此外，慢性暴露于 WTCPM 会导致 AD 小鼠的肠道通透性增加，并改变肠道中细菌组成和功能途径的表达。
我们的结果暗示了肠道-大脑轴之间的复杂相互作用，表明 WTCPM 暴露可能通过潜在机制加剧认知能力下降。确定这些途径为针对急救人员的神经影响提供了进行有针对性干预的机会。
