Nomura Hiroshi, Shimizume Rintaro, Ikegaya Yuji
Department of Cognitive Function and Pathology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Curr Top Behav Neurosci. 2022;59:329-353. doi: 10.1007/7854_2021_253.
In pharmacological studies conducted on animals over the last four decades, histamine was determined to be a strong modulator of learning and memory. Activation of histamine signaling enhances memory consolidation and retrieval. Even long after learning and forgetting, it can still restore the retrieval of forgotten memories. These findings based on animal studies led to human clinical trials with histamine H receptor antagonists/inverse agonists, which revealed their positive effects on learning and memory. Therefore, histamine signaling is a promising therapeutic target for improving cognitive impairments in patients with various neuropsychiatric disorders, including Alzheimer's disease. While the memory-modulatory effects of histamine receptor agonists and antagonists have been confirmed by several research groups, the underlying mechanisms remain to be elucidated. This review summarizes how the activation and inhibition of histamine signaling influence memory processes, introduces the cellular and circuit mechanisms, and discusses the relationship between the human histaminergic system and learning and memory.
在过去四十年对动物进行的药理学研究中，组胺被确定为学习和记忆的强调节剂。组胺信号的激活可增强记忆巩固和检索。即使在学习和遗忘很久之后，它仍能恢复对已遗忘记忆的检索。这些基于动物研究的发现导致了对组胺H受体拮抗剂/反向激动剂的人体临床试验，试验揭示了它们对学习和记忆的积极作用。因此，组胺信号是改善包括阿尔茨海默病在内的各种神经精神疾病患者认知障碍的一个有前景的治疗靶点。虽然组胺受体激动剂和拮抗剂的记忆调节作用已得到多个研究小组的证实，但其潜在机制仍有待阐明。本综述总结了组胺信号的激活和抑制如何影响记忆过程，介绍了细胞和回路机制，并讨论了人类组胺能系统与学习和记忆之间的关系。
