■阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征是细胞外β-淀粉样斑块(Aβ)和细胞内神经原纤维分叉(NFT)的大脑积聚。尽管认知功能下降是AD的疾病定义症状,睡眠功能障碍,通常在认知能力下降之前的常见症状,最近作为AD的核心症状获得了更多的关注。多导睡眠图和其他睡眠测量显示,AD患者的主要发现是睡眠碎片化,N3睡眠缩短,白天过度嗜睡(EDS)和日落。后者反映了唤醒促进神经元(WPNs)的功能障碍,包括位于下丘脑后部的哺乳动物核(TMN)的组胺能神经元(HAN),将有髓鞘的轴突投射到大脑的各个部位。组胺在认知和唤醒中的作用已得到广泛认可。组胺能亚型3和4受体的选择性靶向在AD和衰老的啮齿动物模型中显示出治疗潜力。
■基于PubMed,Scopus,和谷歌学者数据库搜索,这篇综述总结了目前关于组胺能系统在AD和衰老中的知识,它在AD中的治疗潜力,并强调需要更多研究的领域。
■动物研究表明,在AD模型中,组胺能受体或组胺补充剂的药理学操作可改善认知。然而,由于缺乏已知混杂因素的功效或控制,人脑和CSF中HA或HA代谢物水平的测量报告相互矛盾。
■系统研究,包括广泛的年龄,性别,神经病理学诊断,和疾病阶段有必要填补我们目前对人类组胺能神经递质/神经调质系统的理解的空白,尤其是与年龄相关的变化,以及组胺在AD相关功能障碍中的治疗潜力。
UNASSIGNED: Alzheimer\'s disease (AD) is a progressive neurodegenerative disorderfeaturing a brain accumulation of extracellular β-amyloidplaques (Aβ) and intracellular neurofibrillary tautangles (NFTs). Although cognitive decline is a disease-defining symptom of AD, sleep dysfunction, a common symptom often preceding cognitive decline, hasrecently gained more attention as a core AD symptom. Polysomnography and othersleep measures show sleep fragmentation with shortening of N3 sleep togetherwith excessive daytime sleepiness (EDS) and sundowning as the main findings in AD patients. The latter reflects dysfunction of the wake-promoting neurons (WPNs), including histaminergic neurons (HAN) located in thetuberomammillary nucleus (TMN) of the posterior hypothalamus, which projectunmyelinated axons to various parts of the brain.
Histamine\'s role in cognitionand arousal is broadly recognized. Selective targeting of histaminergic subtype-3 and 4 receptors show therapeutic potential in rodent models of AD andaging.
UNASSIGNED: Based on PubMed, Scopus, and google scholar databases search, this
review summarizes the current knowledge on the histaminergic system in AD and aging, its therapeutic potential in AD, and highlight areas where moreresearch is needed.
UNASSIGNED: Animal studies have demonstrated that pharmacological manipulation of histaminergic receptors or
histamine supplementation improves cognition in AD models. However, measurements of HA or HA metabolite levels in the human brainand CSF present contradictory reports due to either lack of power or controls for known confounders.
UNASSIGNED: Systemic studies including broad age, sex, neuropathological diagnosis, and disease stage are warranted to fill the gap in our current understanding of the histaminergic neurotransmitter/neuromodulator system in humans, especially age-related changes, and therapeuticpotential of
histamine in AD-related dysfunction.