title: Aging-associated excess formaldehyde leads to spatial memory deficits.
abstract: Recent studies show that formaldehyde participates in DNA demethylation/methylation cycle. Emerging evidence identifies that neuronal activity induces global DNA demethylation and re-methylation; and DNA methylation is a critical step for memory formation. These data suggest that endogenous formaldehyde may intrinsically link learning-responsive DNA methylation status and memory formation. Here, we report that during spatial memory formation process, spatial training induces an initial global DNA demethylation and subsequent re-methylation associated with hippocampal formaldehyde elevation then decline to baseline level in Sprague Dawley rats. Scavenging this elevated formaldehyde by formaldehyde-degrading enzyme (FDH), or enhancing DNA demethylation by a DNA demethylating agent, both led to spatial memory deficits by blocking DNA re-methylation in rats. Furthermore, we found that the normal adult rats intrahippocampally injected with excess formaldehyde can imitate the aged-related spatial memory deficits and global DNA methylation decline. These findings indicate that aging-associated excess formaldheyde contributes to cognitive decline during aging.
authors: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Zhiqian
authors: Z
authors: Tong
authors: Chanshuai
authors: C
authors: Han
authors: Wenhong
authors: W
authors: Luo
authors: Hui
authors: H
authors: Li
authors: Hongjun
authors: H
authors: Luo
authors: Min
authors: M
authors: Qiang
authors: Tao
authors: T
authors: Su
authors: Beibei
authors: B
authors: Wu
authors: Ying
authors: Y
authors: Liu
authors: Xu
authors: X
authors: Yang
authors: You
authors: Y
authors: Wan
authors: Dehua
authors: D
authors: Cui
authors: Rongqiao
authors: R
authors: He
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004202:Disinfectants / Q000008:administration & dosage / Q000494:pharmacology; D004594:Electrophysiology; D005557:Formaldehyde / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004202:Disinfectants; D005557:Formaldehyde; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases
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