Dpt Pharmacology and Toxicology, University of Navarra, 31008, Pamplona, Spain; IdISNA, Navarra Institute for Health Research, 31008, Pamplona, Spain.
Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Alzheimer Center Groningen, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
Neurochem Int. 2021 Nov;150:105185. doi: 10.1016/j.neuint.2021.105185. Epub 2021 Sep 21.
Even though the involvement of serotonin (5-hydroxytryptamine; 5-HT) and its receptors in Alzheimer's disease (AD) is widely accepted, data on the expression and the role of 5-HT receptors in AD is relatively limited. Therefore, the objective of the present work was to study the expression of serotonergic 5-HT receptors in postmortem samples of AD brains and correlate it with neurotransmitter levels, cognition and behavior. The study population consisted of clinically well-characterized and neuropathologically confirmed AD patients (n = 42) and age-matched control subjects (n = 18). Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and high-performance liquid chromatography were performed on Brodmann area (BA) 7, BA10, BA22, BA24, hippocampus, amygdala, thalamus and cerebellum to measure mRNA levels of 5-HT receptors (HTR7), as well as the concentrations of various monoamine neurotransmitters and their metabolites. Decreased levels of HTR7 mRNA were observed in BA10. A significant association was observed between HTR7 levels in BA10 and BEHAVE-AD cluster B (hallucinations) (rs(28) = 0.444, P < 0.05). In addition, a negative correlation was observed between HTR7 levels in BA10 and both MHPG concentrations in this brain region (rs(45) = -0.311; P < 0.05), and DOPAC levels in the amygdala (rs(42) = -0.311; P < 0.05). Quite surprisingly, no association was found between HTR7 levels and cognitive status. Altogether, this study supports the notion of the involvement of 5-HT receptors in psychotic symptoms in AD, suggesting the interest of testing antagonist acting at this receptor to specifically treat psychotic symptoms in this illness.
尽管涉及血清素（5-羟色胺；5-HT）及其受体在阿尔茨海默病（AD）中的作用已被广泛接受，但关于 5-HT 受体在 AD 中的表达和作用的数据相对有限。因此，本工作的目的是研究 AD 脑死后体样本中 5-羟色胺能 5-HT 受体的表达，并将其与神经递质水平、认知和行为相关联。研究人群包括临床特征明确和神经病理学证实的 AD 患者（n=42）和年龄匹配的对照组（n=18）。采用逆转录定量聚合酶链反应（RT-qPCR）和高效液相色谱法，对 Brodmann 区（BA）7、BA10、BA22、BA24、海马体、杏仁核、丘脑和小脑进行检测，以测量 5-HT 受体（HTR7）的 mRNA 水平，以及各种单胺神经递质及其代谢物的浓度。在 BA10 中观察到 HTR7 mRNA 水平降低。在 BA10 中 HTR7 水平与 BEHAVE-AD 聚类 B（幻觉）（rs(28)=0.444，P<0.05）之间存在显著相关性。此外，在 BA10 中 HTR7 水平与该脑区 MHPG 浓度呈负相关（rs(45)=-0.311；P<0.05），与杏仁核中 DOPAC 水平呈负相关（rs(42)=-0.311；P<0.05）。令人惊讶的是，HTR7 水平与认知状态之间没有相关性。总的来说，这项研究支持 5-HT 受体参与 AD 中的精神病症状的观点，表明测试针对该受体的拮抗剂以专门治疗这种疾病中的精神病症状具有一定的研究价值。
