Long-term Air Pollution Exposure Is Associated with Neuroinflammation, an Altered Innate Immune Response, Disruption of the Blood-Brain Barrier, Ultrafine Particulate Deposition, and Accumulation of Amyloid β-42 and α-Synuclein in Children and Young Adults
Long-term Air Pollution Exposure Is Associated with Neuroinflammation, an Altered Innate Immune Response, Disruption of the Blood-Brain Barrier, Ultrafine Particulate Deposition, and Accumulation of Amyloid β-42 and α-Synuclein in Children and Young Adults
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DOI：
10.1177/0192623307313011
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发表时间：
2008-02-01
影响因子：
1.5
通讯作者：
Reed, William
中科院分区：
文献类型：
--
作者：
Calderon-Garciduenas, Lilian;Solt, Anna C.;Reed, William
空气污染是一个严重的环境问题。我们调查了居住在空气污染严重的城市是否与突然死亡的健康儿童和年轻人的神经炎症/神经变性有关。我们从25.1+/-1.5岁的低暴露(n=12)或高暴露(n=35)的居民中检测了靶脑区环氧合酶-2、白介素1β和CD14的mRNA。在高度暴露的受试者中，嗅球、额叶皮质、黑质和迷走神经中环氧合酶-2、白介素1β和CD14表达上调；血脑屏障破坏；内皮细胞激活、氧化应激和炎性细胞运输。在载脂蛋白E(ApoE)3/3和25岁的受试者中，58.8%的受试者和4岁的受试者中观察到Aβ42(Aβ42)免疫反应阳性，而在25岁受试者中，23.5%的受试者中观察到α-突触核蛋白。在嗅球神经元中可以观察到颗粒物质(PM)，在肺、额叶和三叉神经节毛细血管的管腔内红细胞中可以观察到PM<；100 nm。暴露在空气污染中会导致神经炎症，改变大脑的先天免疫反应，并从童年开始积累Aβ42和α-突触核蛋白。暴露在空气污染中应该被认为是阿尔茨海默氏症和帕金森氏症的风险因素，如果APOE 4等位基因携带者生活在污染的环境中，他们患阿尔茨海默病的风险可能会更高。
Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1 beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1 beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta 42 (A beta 42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries.Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of A beta 42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.