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基于小鼠和人类线索的二甲基亚硝胺暴露与认知障碍的关联

Association of -nitrosodimethylamine exposure with cognitive impairment based on the clues of mice and humans.

作者信息

Liu Wei, Huang Jia, Yan Zhi, Lin Yankui, Huang Guanqin, Chen Xiao, Wang Zhou, Spencer Peter S, Liu Jianjun

机构信息

Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020-2024), Shenzhen Center for Disease Control and Prevention, Shenzhen, China.

Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China.

出版信息

Front Aging Neurosci. 2023 Jun 27;15:1137164. doi: 10.3389/fnagi.2023.1137164. eCollection 2023.

Abstract

-nitrosodimethylamine (NDMA) is an environmental and food contaminant, but limited data to concern whether NDMA has adverse effects on the brain. This study first determined the concentration of NDMA in foods from aquaculture markets in Shenzhen, then analyzed the effects on C57BL/6 mice and further evaluated on the urine samples of elderly Chinese residents with normal cognition (NC, = 144), cognitive decline (CD, = 116) and mild cognitive impairment (MCI, = 123). The excessive rate of NDMA in foods was 3.32% (27/813), with a exceeding range of 4.78-131.00 μg/kg. Behavioral tests showed that 60 days treatment of mice with 3 mg/kg NDMA reduced cognitive performance. Cognitive impairment in human was significantly associated with sex, educational levels, length of residence in Shenzhen, household registration, passive smoking, rice, fresh vegetables, bacon products. NDMA was detected in 55.4% (212/383) of urine samples, with a median concentration of 0.23 μg/L (1.20 × 10 -157.39 μg/L). The median concentration for NC, CD and MCI were 0.32, 0.27, and 0 μg/L, respectively. The urinary NDMA concentration had a strong negative correlation with cognitive impairment ( = -0.89, = 0.024). The median estimated daily intake (EDI) of NDMA was determined to be 6.63 ng/kg-bw/day. Taken together, there appears to be an association between NDMA and human and murine cognition, which provides a new clue to Alzheimer's disease (AD).

摘要

N-亚硝基二甲胺(NDMA)是一种环境和食品污染物,但关于NDMA是否对大脑有不良影响的数据有限。本研究首先测定了深圳水产市场食品中NDMA的浓度,然后分析其对C57BL/6小鼠的影响,并进一步对认知正常的中国老年居民(NC,n = 144)、认知衰退(CD,n = 116)和轻度认知障碍(MCI,n = 123)的尿液样本进行评估。食品中NDMA的超标率为3.32%(27/813),超标范围为4.78 - 131.00μg/kg。行为测试表明,用3mg/kg NDMA处理小鼠60天会降低认知能力。人类的认知障碍与性别、教育程度、在深圳的居住时间、户籍、被动吸烟、大米、新鲜蔬菜、培根制品显著相关。在55.4%(212/383)的尿液样本中检测到了NDMA,中位浓度为0.23μg/L(1.20×10 - 157.39μg/L)。NC、CD和MCI的中位浓度分别为0.32、0.27和0μg/L。尿NDMA浓度与认知障碍呈强负相关(r = -0.89,P = 0.024)。NDMA的中位估计每日摄入量(EDI)确定为6.63ng/kg-bw/天。综上所述,NDMA与人类和小鼠的认知之间似乎存在关联,这为阿尔茨海默病(AD)提供了新线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bfc/10333700/42d713117a8a/fnagi-15-1137164-g001.jpg

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