失われた記憶の回復—ヒスタミン神経系による記憶想起の調節について

Recovery of Forgotten Memories: Modulation of Memory Recall by Brain Histamine System

過去の出来事を思い出せないときでも，その記憶の痕跡は脳内に残っていると考えられるが，自由に記憶痕跡を再活性化して想起を促進する方法は存在しない。中枢ヒスタミンは記憶・学習を調節する生理活性物質として注目されている。本総説では，中枢ヒスタミン神経系の概要と，ヒスタミンと記憶・学習の関係，特にヒスタミンによる記憶想起の促進について概説する。

Abstract

Even after memories fade they may persist latently in the brain. However, there are no clinically applicable methods for reactivating memory traces and promoting memory retrieval. In the brain histamine modulates learning and memory, sleep and wakefulness, feeding, drinking, and neuroendocrine functions. Animal studies demonstrated that histamine H₃ receptor inverse agonists enhance histamine release in the brain and promote learning and memory. In particular, the H₃ receptor inverse agonists induce recall of forgotten memories—possibly by facilitating reactivation of memory engram cells. Therefore, H₃ receptors are a promising targets for treating cognitive dysfunction. While past clinical trials failed to find beneficial effects of H₃ receptor inverse agonists on learning and memory, a recent study showed that inverse agonists enhance memory retrieval in a participant-dependent manner. This review describes the brain's histaminergic system and the modulation of learning and memory by histamine.