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Agerelated formaldehyde interferes with DNA methyltransferase function causing memory loss in Alzheimers disease
Zhiqian Tong1,2; Chanshuai Han1,3; Min Qiang1,3; Weishan Wang4; Jihui Lv4; Shouzi Zhang4; \Wenhong Luo5; Hui Li5; Hongjun Luo5; Jiangning Zhou6; Beibei Wu1,3; Tao Su1,3; Xu Yang7; Xiaomin Wang2; Ying Liu1; Rongqiao He1,2,7; R. He
第一作者Zhiqian Tong
2015
发表期刊Neurobiology of Aging
通讯作者邮箱herq@sun5.ibp.ac.cn
卷号36期号:1页码:100-110
摘要

Hippocampus-related topographic amnesia is the most common symptom of memory disorders in Alzheimer’s disease (AD) patients. Recent studies have revealed that experience-mediated DNA methylation, which is regulated by enzymes with DNA methyltransferase (DNMT) activity, is required for the formation of recent memory as well as the maintenance of remote memory. Notably, overexpression of DNMT3a in the hippocampus can reverse spatial memory deficits in aged mice. However, a decline in global DNA methylation was found in the autopsied hippocampi of patients with AD. Exactly, what endogenous factors that affect DNA methylation still remain to be elucidated. Here, we report a marked increase in endogenous formaldehyde levels is associated with a decline in global DNA methylation in the autopsied hippocampus from AD patients. In vitro and in vivo results show that formaldehyde in excess of normal physiological levels reduced global DNA methylation by interfering DNMTs. Interestingly, intrahippocampal injection of excess formaldehyde before spatial learning in healthy adult rats can mimic the learning difficulty of early stage of AD. Moreover, injection of excess formaldehyde after spatial learning can mimic the loss of remote spatial memory observed in late stage of AD. These findings suggest that aging-associated formaldehyde contributes to topographic amnesia in AD patients.

关键词Endogenous formaldehyde DNA methyltransfarases (DNMTs Topographic amnesia Alzheimer’s disease (AD)
收录类别SCI
语种英语
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/25594
专题脑与认知科学国家重点实验室
通讯作者R. He
作者单位1.State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
2.Alzheimer’s Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
3.University of the Chinese Academy of Sciences, Beijing, China
4.Beijing Geriatric Hospital, Beijing, China
5.Beijing Geriatric Hospital, Beijing, China e Central Laboratory, Shantou University Medical College, Guangdong, China
6.University of Science and Technology of China, Anhui, China
7.Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Huazhong Normal University, Wuhan, China
8.Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
推荐引用方式
GB/T 7714
Zhiqian Tong,Chanshuai Han,Min Qiang,et al. Agerelated formaldehyde interferes with DNA methyltransferase function causing memory loss in Alzheimers disease[J]. Neurobiology of Aging,2015,36(1):100-110.
APA Zhiqian Tong.,Chanshuai Han.,Min Qiang.,Weishan Wang.,Jihui Lv.,...&R. He.(2015).Agerelated formaldehyde interferes with DNA methyltransferase function causing memory loss in Alzheimers disease.Neurobiology of Aging,36(1),100-110.
MLA Zhiqian Tong,et al."Agerelated formaldehyde interferes with DNA methyltransferase function causing memory loss in Alzheimers disease".Neurobiology of Aging 36.1(2015):100-110.
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