Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
University of Ljubljana, Faculty of Medicine, Institute of Pharmacology and Experimental Toxicology, Korytkova 2, 1000 Ljubljana, Slovenia.
Psychol Med. 2023 Dec;53(16):7537-7549. doi: 10.1017/S0033291723001265. Epub 2023 May 25.
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is involved in the stress response and may play a key role in mood disorders, but no information is available on PACAP for the human brain in relation to mood disorders.
PACAP-peptide levels were determined in a major stress-response site, the hypothalamic paraventricular nucleus (PVN), of people with major depressive disorder (MDD), bipolar disorder (BD) and of a unique cohort of Alzheimer's disease (AD) patients with and without depression, all with matched controls. The expression of PACAP-(Adcyap1mRNA) and PACAP-receptors was determined in the MDD and BD patients by qPCR in presumed target sites of PACAP in stress-related disorders, the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC).
PACAP cell bodies and/or fibres were localised throughout the hypothalamus with differences between immunocytochemistry and hybridisation. In the controls, PACAP-immunoreactivity-(ir) in the PVN was higher in women than in men. PVN-PACAP-ir was higher in male BD compared to the matched male controls. In all AD patients, the PVN-PACAP-ir was lower compared to the controls, but higher in AD depressed patients compared to those without depression. There was a significant positive correlation between the Cornell depression score and PVN-PACAP-ir in all AD patients combined. In the ACC and DLPFC, alterations in mRNA expression of PACAP and its receptors were associated with mood disorders in a differential way depending on the type of mood disorder, suicide, and psychotic features.
The results support the possibility that PACAP plays a role in mood disorder pathophysiology.
垂体腺苷酸环化酶激活肽（PACAP）参与应激反应，可能在心境障碍中发挥关键作用，但目前尚无关于人类大脑中与心境障碍相关的 PACAP 的信息。
在主要应激反应部位下丘脑室旁核（PVN）中测定了患有重度抑郁症（MDD）、双相情感障碍（BD）的人和具有和不具有抑郁症的独特阿尔茨海默病（AD）患者的 PACAP-肽水平，所有这些患者都有匹配的对照组。通过 qPCR 测定了 MDD 和 BD 患者中 PACAP-（Adcyap1mRNA）和 PACAP 受体的表达，在应激相关障碍的假定 PACAP 靶位，即背外侧前额叶皮质（DLPFC）和前扣带皮质（ACC）中。
PACAP 细胞体和/或纤维定位于整个下丘脑，免疫细胞化学和杂交之间存在差异。在对照组中，PVN 中的 PACAP 免疫反应性（ir）在女性中高于男性。与匹配的男性对照组相比，男性 BD 的 PVN-PACAP-ir 更高。在所有 AD 患者中，PVN-PACAP-ir 均低于对照组，但 AD 抑郁患者高于无抑郁患者。在所有 AD 患者中，PVN-PACAP-ir 与 Cornell 抑郁评分之间存在显著正相关。在 ACC 和 DLPFC 中，PACAP 及其受体的 mRNA 表达的改变与心境障碍相关，其方式取决于心境障碍的类型、自杀和精神病特征。
这些结果支持 PACAP 可能在心境障碍发病机制中发挥作用的可能性。
