Institute of Brain Science and Disease, Qingdao University, Qingdao, 266071, China.
Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao, 266071, China.
Sci Rep. 2024 Feb 14;14(1):3721. doi: 10.1038/s41598-024-54066-0.
Parkinson's disease (PD) is the second most common age-related neurodegenerative disease, with a progressive loss of dopaminergic cells and fibers. The purpose of this study was to use different doses of 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB) of mice to mimic the different stages of the disease and to characterize in detail their motor and non-motor behavior, as well as neuropathological features in the nigrostriatal pathway. MFB were injected with 0.5 μg, 1 μg, 2 μg of 6-OHDA using a brain stereotaxic technique. 6-OHDA induced mitochondrial damage dose-dependently, as well as substantia nigra pars compacta (SNpc) tyrosine hydroxylase-positive (TH) cell loss and striatal TH fiber loss. Activation of astrocytes and microglia in the SNpc and striatum were consistently observed at 7 weeks, suggesting a long-term glial response in the nigrostriatal system. Even with a partial or complete denervation of the nigrostriatal pathway, 6-OHDA did not cause anxiety, although depression-like behavior appeared. Certain gait disturbances were observed in 0.5 μg 6-OHDA lesioned mice, and more extensive in 1 μg group. Despite the loss of more neurons from 2 μg 6-OHDA, there was no further impairment in behaviors compared to 1 μg 6-OHDA. Our data have implications that 1 μg 6-OHDA was necessary and sufficient to induce motor and non-motor symptoms in mice, thus a valuable mouse tool to explore disease progression and new treatment in PD.
帕金森病（PD）是第二常见的与年龄相关的神经退行性疾病，其特征是多巴胺能细胞和纤维进行性丧失。本研究的目的是使用不同剂量的 6-羟多巴胺（6-OHDA）注射到内侧前脑束（MFB）来模拟疾病的不同阶段，并详细描述其运动和非运动行为以及黑质纹状体通路的神经病理学特征。使用脑立体定向技术将 MFB 注射 0.5μg、1μg、2μg 的 6-OHDA。6-OHDA 诱导的线粒体损伤呈剂量依赖性，以及黑质致密部（SNpc）酪氨酸羟化酶阳性（TH）细胞丢失和纹状体 TH 纤维丢失。在 7 周时， consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed consistently observed the activation of astrocytes and microglia in the SNpc and striatum， suggesting a long-term glial response in the nigrostriatal system. 尽管黑质纹状体通路部分或完全去神经支配，但抑郁样行为出现，但不会导致焦虑。在 0.5μg 6-OHDA 损伤的小鼠中观察到某些步态障碍，而在 1μg 组中更为广泛。尽管来自 2μg 6-OHDA 的神经元损失更多，但与 1μg 6-OHDA 相比，行为没有进一步受损。我们的数据表明，1μg 6-OHDA 足以诱导小鼠的运动和非运动症状，因此是探索 PD 疾病进展和新治疗方法的有价值的小鼠工具。
