基础科学和病原发生学
Leandro Ceotto Freitas Lima1, Kevin P Kotredes2, Juliet A Moncaster3
1Indiana University School of Medicine, Indianapolis, IN, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
概括
,和等环境毒素在大脑中积累,改变基因表达,增加阿尔茨海默氏症.
科学领域:
- 神经科学是一个神经科学.
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
背景情况:
- 阿尔茨海默病 (AD) 和与AD相关的痴呆症 (ADRD) 与环境毒素有关,但机制尚不清楚.
- 阿尔茨海默病的遗传风险变体可以与神经毒性金属 (,) 和金属化物 () 暴露产生协同作用.
- 这些有毒物质穿越血脑屏障 (BBB),破坏神经元功能,并调节AD通路.
研究的目的:
- 研究 (Pb), (Cd) 和 (As) 暴露如何改变与AD相关的基因表达.
- 为了确定这些暴露是否以毒素特异性和年龄依赖的方式增强AD病原性.
- 建立TOX-AD联盟,作为AD/ADRD研究的暴露组资源.
主要方法:
- 模型AD小鼠通过饮用水暴露在Pb,Cd或As中30天.
- 一个单独的B6.APPSwDI小鼠队列被暴露在Pb中,以评估BBB完整性.
- 收集了血液和大脑组织,用于毒性水平分析和基因表达概况.
主要成果:
- 暴露动物在血液和大脑中显示金属/金属化物水平增加.
- 基因表达的变化包括增加的VGF (Pb,As) 和减少的APP (Cd).
- Pb暴露破坏了BBB完整性,增加了Aβ比率,并促进了Aβ沉积,与AD病理学相关的Pb,As和Cd的显著基因本体学关联.
结论:
- 暴露于Pb,Cd和As会导致毒素在血液和大脑中的积累.
- 这些暴露会诱导与AD相关的基因表达的毒剂特异性变化.
- 这些发现突显了环境毒素在AD病理生物学中的作用.
相关概念视频
Infection
11.6K
When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
11.6K
Urinary Tract Infection II: Pathophysiology
524
The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
524
Cystic Fibrosis: Pathogenesis
676
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
676
Pneumonia II: Pathophysiology
2.5K
The pathophysiology of pneumonia involves the following steps:
2.5K
Stages of Infection
64.7K
Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
64.7K
Defense Against Bacterial Pathogens
2.6K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
2.6K


