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内源性甲醛参与调节记忆

费学超, 童志前^*

首都医科大学北京脑重大疾病研究院，北京 100069

摘要

甲醛是地球上进化早期阶段最早出现的同时含有C、H、O元素的最简单有机小分子之一，被发现存在于每一个真核细胞中，并参与“一碳代谢”。近期研究表明，内源性甲醛可能作为信号分子参与记忆的形成。电刺激或学习训练后，大鼠脑内甲醛含量瞬时升高，激活N-甲基-D-天冬氨酸(N-methyl-D-aspartate, NMDA)受体，促进长时程增强(long-term potentiation,LTP)或空间记忆的形成。相反，降低脑内甲醛含量后，NMDA受体不能被激活，不能形成LTP和短时记忆。在正常老年大鼠和阿尔茨海默病转基因小鼠中，脑内甲醛浓度异常升高，NMDA受体活性受到抑制，空间记忆受损。因此，维持体内生理水平的甲醛浓度对于记忆的形成与储存尤为必要。本文对内源性甲醛在学习和记忆中的生理与病理生理学功能进行了综述。

关键词： 内源性甲醛; 阿尔茨海默病; NMDA受体; 长时程增强; 空间记忆

分类号：Q42; R742

Endogenous formaldehyde regulates memory

FEI Xue-Chao, TONG Zhi-Qian^*

Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, China

Abstract

Formaldehyde is one of the simplest organic small molecules containing C, H and O elements in the early stage of earth’s evolution; however, it has been found to be existed in every eukaryotic cell and participate in “one carbon metabolism”. Recent studies have shown that formaldehyde may act as a signal molecule to regulate memory formation. After electrical stimulation or learning activity, the levels of formaldehyde in rat brains were increased instantly, and N-methyl-D-aspartate (NMDA) receptor was activated to promote the formation of long-term potentiation (LTP) or spatial memory. On the contrary, after reducing the levels of formaldehyde in the brains, NMDA receptor could not be activated, which was accompanied by the deficits in both LTP and memory. Moreover, in the brains of normal aged rats and APP/PS1 transgenic mice, the concentrations of formaldehyde were abnormally increased, which directly inhibited NMDA receptor activity and impaired spatial memory. This article reviewed the physiological and pathophysiological functions of endogenous formaldehyde in learning and memory.

Key words: endogenous formaldehyde; Alzheimer’s disease; N-methyl-D-aspartate receptor; long-term potentiation; spatial memory

收稿日期：2019-05-20　　录用日期：2019-08-15

通讯作者：童志前　　E-mail: tzqbeida@ccmu.edu.cn

DOI: 10.13294/j.aps.2020.0026

引用本文：

费学超, 童志前. 内源性甲醛参与调节记忆[J]. 生理学报 2020; 72 (4): 463-474.

FEI Xue-Chao, TONG Zhi-Qian. Endogenous formaldehyde regulates memory. Acta Physiol Sin 2020; 72 (4): 463-474 (in Chinese with English abstract).