title: Accumulated hippocampal formaldehyde induces age-dependent memory decline.
abstract: Aging is an important factor in memory decline in aged animals and humans and in Alzheimer's disease and is associated with the impairment of hippocampal long-term potentiation (LTP) and down-regulation of NR1/NR2B expression. Gaseous formaldehyde exposure is known to induce animal memory loss and human cognitive decline; however, it is unclear whether the concentrations of endogenous formaldehyde are elevated in the hippocampus and how excess formaldehyde affects LTP and memory formation during the aging process. In the present study, we report that hippocampal formaldehyde accumulated in memory-deteriorating diseases such as age-related dementia. Spatial memory performance was gradually impaired in normal Sprague-Dawley rats by persistent intraperitoneal injection with formaldehyde. Furthermore, excess formaldehyde treatment suppressed the hippocampal LTP formation by blocking N-methyl-D-aspartate (NMDA) receptor. Chronic excess formaldehyde treatment over a period of 30 days markedly decreased the viability of the hippocampus and down-regulated the expression of the NR1 and NR2B subunits of the NMDA receptor. Our results indicate that excess endogenous formaldehyde is a critical factor in memory loss in age-related memory-deteriorating diseases.
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Graduate University of the Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Tong
authors.forename: Chanshuai
authors.initials: C
authors.lastname: Han
authors.forename: Wenhong
authors.initials: W
authors.lastname: Luo
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Hongjun
authors.initials: H
authors.lastname: Luo
authors.forename: Jiangning
authors.initials: J
authors.lastname: Zhou
authors.forename: Jinshun
authors.initials: J
authors.lastname: Qi
authors.forename: Rongqiao
authors.initials: R
authors.lastname: He
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D005557:Formaldehyde / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007267:Injections; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde