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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
AbstractAlzheimer'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.
KeywordAlzheimer's Disease Enzymes Formaldehyde Metabolism Samp8 Samr1 Ssao Adh3
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WOS IDWOS:000336262000021
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Cited Times:25[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.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
First Author Affilication脑与认知科学国家重点实验室
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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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