利血平诱导帕金森病模型中的 5-羟色胺能功能障碍。
Serotonergic dysfunction in a model of parkinsonism induced by reserpine.
机构信息
Behavioral and Evolutionary Neurobiology Laboratory, Department of Physiology, Federal University of Sergipe, São Cristovão, 49100-000, SE, Brazil; Post-Graduate Program of Dentistry, Federal University of Sergipe, Aracaju, 49060-100, SE, Brazil.
Behavioral and Evolutionary Neurobiology Laboratory, Department of Physiology, Federal University of Sergipe, São Cristovão, 49100-000, SE, Brazil.
出版信息
J Chem Neuroanat. 2019 Mar;96:73-78. doi: 10.1016/j.jchemneu.2018.12.011. Epub 2018 Dec 28.
Parkinson's disease (PD) is mainly characterized by a dopamine deficiency accompanied by structural and functional changes in striatal neuronal projections. However, studies have considered PD as a multi-systemic disease in which the neurodegenerative process extends beyond the dopaminergic system. Therefore, the purpose of the present study was to investigate the time-course of serotonergic neuron damage in a progressive model of parkinsonism induced by a low dose of reserpine. Thus, male Wistar rats received 4 (ST, short-treatment of reserpine) or 10 (MT, middle-term treatment of reserpine) subcutaneous injections of vehicle or reserpine (0.1 mg/kg) at a volume of 1 mL/kg body weight, on alternate days. Animals were euthanized 48 h after the last injection for immunohistochemical analysis. After ST, 5-HT immunoreactivity decreased in hippocampal subareas (CA1 and CA3) and medial prefrontal cortex (mPFC) compared to vehicle. Furthermore, animals MT-treated also showed progressive decrease of 5-HT immunoreactivity in CA1 and CA3 subareas. Conversely, a significant increase of 5-HT immunoreactivity was found in mPFC and dorsal raphe nucleus (DRN) in animals submitted to MT when compared to ST exposure. The results showed that, in the repeated low-dose reserpine rat model, variations in the immunoreactivity of 5-HT start early in the course of progressive parkinsonism.
帕金森病（PD）主要表现为多巴胺缺乏，并伴有纹状体神经元投射的结构和功能变化。然而，研究认为 PD 是一种多系统疾病，神经退行性过程不仅局限于多巴胺能系统。因此，本研究旨在探讨低剂量利血平诱导的进行性帕金森病模型中 5-羟色胺能神经元损伤的时程。雄性 Wistar 大鼠隔日接受 4（ST，利血平短期处理）或 10（MT，利血平中期处理）次皮下注射溶剂或利血平（0.1mg/kg），每次 1ml/kg 体重。最后一次注射后 48 小时处死动物进行免疫组织化学分析。与溶剂组相比，ST 后海马亚区（CA1 和 CA3）和内侧前额叶皮质（mPFC）中的 5-HT 免疫反应性降低。此外，MT 处理的动物也表现出 CA1 和 CA3 亚区 5-HT 免疫反应性的进行性下降。相反，与 ST 暴露相比，MT 处理的动物 mPFC 和中缝背核（DRN）中的 5-HT 免疫反应性显著增加。结果表明，在重复低剂量利血平大鼠模型中，5-HT 免疫反应性的变化在进行性帕金森病的早期就开始出现。
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