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A Novel Mechanism for Endogenous Formaldehyde Elevation in SAMP8 Mouse
Qiang, Min1,3; Xiao, Rong1,4; Su, Tao1,3; Wu, Bei-Bei1; Tong, Zhi-Qian1; Liu, Ying1; He, Rong-Qiao1,2
2014
发表期刊JOURNAL OF ALZHEIMERS DISEASE
ISSN1387-2877
文章类型Article
卷号40期号:4页码:1039-1053
摘要Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people worldwide. Increasing evidence suggests that formaldehyde might be one of the various pathological mechanisms involved in the process of AD onset. Here, we use an AD mouse model, senescence accelerated mouse-prone 8 strain (SAMP8), to study the relationship between endogenous formaldehyde and impairment of cognition. The Morris water maze test was used to evaluate the spatial learning and memory ability of 3-month-old SAMP8 mice, and we correlated the results with endogenous formaldehyde concentrations in the brain. To investigate the underlying reasons for formaldehyde elevation in neurodegenerative diseases, the expression levels of enzymes involved in formaldehyde metabolism were analyzed, including (anabolic) semicarbazide sensitive amine oxidase (SSAO) and (catabolic) alcohol dehydrogenase III (ADH3). When compared with age-matched SAMR1 mice, we found that in 3-month-old SAMP8 mice the capacity for spatial learning and memory was lower, while brain formaldehyde levels were higher. By using real-time PCR, western blotting, enzyme assay, and immunohistochemistry techniques, we discovered that SSAO expression levels were increased, whereas ADH3 exhibited reduced expression levels of mRNA, protein, and enzyme activity. The imbalance of these metabolic enzymes may represent a causal explanation for the observed formaldehyde elevation in the SAMP8 brain. Such increase could be responsible for the observed tau hyperphosphorylation assumed to result in protein aggregation, ultimately leading to cognitive impairment. Taken together, our study gives new insights into the role of metabolic enzymes in age-related accumulation of formaldehyde, and thus the establishment of neurodegenerative diseases.
关键词Alzheimer's Disease Enzymes Formaldehyde Metabolism Samp8 Samr1 Ssao Adh3
收录类别SCI
语种英语
WOS记录号WOS:000336262000021
引用统计
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/13449
专题中国科学院心理健康重点实验室
作者单位1.Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Liaoning Normal Univ, Sch Life Sci, Dalian, Peoples R China
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GB/T 7714
Qiang, Min,Xiao, Rong,Su, Tao,et al. A Novel Mechanism for Endogenous Formaldehyde Elevation in SAMP8 Mouse[J]. JOURNAL OF ALZHEIMERS DISEASE,2014,40(4):1039-1053.
APA Qiang, Min.,Xiao, Rong.,Su, Tao.,Wu, Bei-Bei.,Tong, Zhi-Qian.,...&He, Rong-Qiao.(2014).A Novel Mechanism for Endogenous Formaldehyde Elevation in SAMP8 Mouse.JOURNAL OF ALZHEIMERS DISEASE,40(4),1039-1053.
MLA Qiang, Min,et al."A Novel Mechanism for Endogenous Formaldehyde Elevation in SAMP8 Mouse".JOURNAL OF ALZHEIMERS DISEASE 40.4(2014):1039-1053.
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