Departamento de Neurologia/Neurociência, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), Av. Pedro de Toledo, 699, 1º andar, São Paulo, SP, Brazil.
Departamento de Psicobiologia, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, SP, Brazil.
Pharmacol Rep. 2020 Apr;72(2):296-304. doi: 10.1007/s43440-020-00074-6. Epub 2020 Mar 2.
Cardiovascular dysfunctions are common non-motor symptoms in patients with Parkinson's disease (PD) that can result in reduced quality of life and even death. Research in animal models designed to characterize the pathological association between PD and cardiovascular abnormalities is still in its infancy. This study assessed the early impact of the nigrostriatal dopaminergic damage on cardiological features in the unilateral 6-OHDA rat model of PD.
Male Wistar rats received unilateral intrastriatal injections of 6-OHDA and sham rats were injected with saline. Animals were studied 15 days later. Immunohistochemistry was used for visualization of tyrosine hydroxylase (TH)-positive neurons in the nigrostriatal system. Electrocardiogram recordings of heart rate were performed in conscious rats. Heart levels of vitamin D, inflammatory cytokines and C-reactive protein were assessed through electrochemiluminescence immunoassay, quantitative reverse transcription PCR and turbidimetric method, respectively.
We found a post-injury reduction of TH-immunoreactivity of approximately 45% in the substantia nigra pars compacta and 20% in the striatum. Heart rate reduction was found in 6-OHDA-lesioned rats as compared with sham counterparts. Reduced levels of vitamin D and increased levels of inflammatory factors (C-reactive protein, IL-6, TNF-α and TGF-β) were detected in the heart tissue of PD rats in comparison with sham.
Our findings suggest a link between cardiac tissue changes and cardiac functional changes early after the central dopaminergic damage induced by 6-OHDA. Knowledge of the cardiac abnormalities in the 6-OHDA model is critical in identifying future therapeutic targets and disease-modifying approaches for PD non-motor features.
心血管功能障碍是帕金森病(PD)患者常见的非运动症状,可导致生活质量下降,甚至死亡。用于描述 PD 与心血管异常之间病理关联的动物模型研究仍处于起步阶段。本研究评估了黑质纹状体多巴胺能损伤对单侧 6-OHDA 帕金森病大鼠模型中心血管特征的早期影响。
雄性 Wistar 大鼠接受单侧纹状体 6-OHDA 注射,假手术大鼠注射生理盐水。15 天后对动物进行研究。免疫组织化学用于显示黑质纹状体系统中酪氨酸羟化酶(TH)阳性神经元。在清醒大鼠中进行心电图记录心率。通过电化学发光免疫分析、定量逆转录 PCR 和比浊法分别评估心脏维生素 D、炎症细胞因子和 C 反应蛋白的水平。
我们发现,在黑质致密部,TH 免疫反应性损伤后减少了约 45%,在纹状体减少了 20%。与假手术对照组相比,6-OHDA 损伤大鼠的心率降低。与假手术组相比,PD 大鼠心脏组织中维生素 D 水平降低,炎症因子(C 反应蛋白、IL-6、TNF-α和 TGF-β)水平升高。
我们的发现表明,6-OHDA 诱导的中枢多巴胺能损伤后早期,心脏组织变化与心脏功能变化之间存在关联。了解 6-OHDA 模型中的心脏异常对于确定 PD 非运动特征的未来治疗靶点和疾病修饰方法至关重要。