Hong Xiao-Yue, Li Siwei, Li Tian, Chen Wei, Li Yirong, Wang Zhuo, Luo Yi
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, Hubei, China.
Department of Neurology, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, Hubei, China.
Heliyon. 2024 Oct 2;10(19):e38843. doi: 10.1016/j.heliyon.2024.e38843. eCollection 2024 Oct 15.
The important role of catecholamines has been gradually emphasized in the pathogenesis of neurodegenerative process. As the most prevalent form of cognitive dysfunction, Alzheimer's disease (AD) and vascular dementia (VaD) have the distinct pathological features and pathogenic mechanisms, however, the differential involvement of central and peripheral catecholamines between AD and VaD was still unclear.
Triple-transgenic AD (3 × Tg-AD) mice and chronic cerebral hypoperfusion (CCH) in rats induced by two-vessel occlusion (2VO) were used as the AD and VaD model in this study, respectively. The concentrations of catecholamines (dopamine, epinephrine and norepinephrine) and their metabolites (3-methoxytyramine, metanephrine and normetanephrine) in serum and five brain regions (hippocampus, cortex, corpus striatum, thalamus and pons) from 3 × Tg-AD mice and 2VO rats were quantitatively determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay.
High expression and distribution of hippocampal dopamine, and epinephrine and norepinephrine in the cortex and thalamus were found in the early 3 × Tg-AD model, whereas chronic cerebral hypoperfusion induced by 2VO mainly affected the central noradrenergic and noradrenergic system, but not dopaminergic system. The increased serum levels of catecholamines were investigated in the 2VO rats, but not in the 3 × Tg-AD mice.
The differential expression and distribution of central catecholamines and their metabolites suggests the distinct catecholamines-related pathogenesis between AD and VaD. Peripheral catecholamine surge may be involved in the development of VaD, and the treatment strategy to prevent or reverse the effects of peripheral catecholamines may be protective for VaD.
儿茶酚胺在神经退行性病变发病机制中的重要作用已逐渐得到重视。作为最常见的认知功能障碍形式，阿尔茨海默病（AD）和血管性痴呆（VaD）具有不同的病理特征和致病机制，然而，AD和VaD之间中枢和外周儿茶酚胺的差异参与情况仍不清楚。
本研究分别采用三联转基因AD（3×Tg-AD）小鼠和双侧颈总动脉结扎（2VO）诱导的大鼠慢性脑灌注不足（CCH）作为AD和VaD模型。通过液相色谱-串联质谱（LC-MS/MS）分析法定量测定3×Tg-AD小鼠和2VO大鼠血清及五个脑区（海马、皮质、纹状体、丘脑和脑桥）中儿茶酚胺（多巴胺、肾上腺素和去甲肾上腺素）及其代谢产物（3-甲氧基酪胺、间甲肾上腺素和去甲间肾上腺素）的浓度。
在早期3×Tg-AD模型中发现海马多巴胺以及皮质和丘脑中肾上腺素和去甲肾上腺素的高表达和分布，而2VO诱导的慢性脑灌注不足主要影响中枢去甲肾上腺素能和肾上腺素能系统，而非多巴胺能系统。在2VO大鼠中检测到血清儿茶酚胺水平升高，但在3×Tg-AD小鼠中未检测到。
中枢儿茶酚胺及其代谢产物的差异表达和分布提示AD和VaD之间存在不同的儿茶酚胺相关发病机制。外周儿茶酚胺激增可能参与VaD的发展，预防或逆转外周儿茶酚胺作用的治疗策略可能对VaD具有保护作用。
