Parkinson’s disease has become one of the most common neurodegenerative diseases. Pathological changes typically manifest following dopaminergic neuron loss in the substantia nigra and abnormal alpha-synuclein (α-syn) aggregation in the neurons. α-Syn is the major component of Lewy bodies. However, research pertaining to the spread of abnormal α-syn aggregations, which results in specific damage to the brain structure and function, is lacking. In the present study, full-length human α-syn fibrils were injected into the medial forebrain bundle of rats, with an experimental endpoint of 6 months. Histological analysis was conducted to observe the pathological progress of abnormal endogenous α-syn aggregation and nerve fiber quality. Changes in gray and white matter integrity were quantitatively analyzed using voxel-based morphometry (VBM). Behavioral changes were observed over the 6-month period. Histological analysis showed reduced dopamine transporter levels in the striatum of the experimental rats; widespread abnormal endogenous α-syn accumulation; and damaged, sparse, and disordered nerve fibers in the experimental group. VBM showed that at 6 months after surgery, bilateral anterior limbic, bilateral inferior limbic, right hippocampal, and right cortical volumes had reduced, whereas thalamic volume had increased in the experimental group compared with that in the control group. Damage to the limbic and thalamic fiber structure may occur in the earlier stages of Parkinson’s disease.

帕金森病已成为最常见的神经退行性疾病之一。病理变化通常表现在黑质中多巴胺能神经元丢失和神经元中异常 α-突触核蛋白 (α-syn) 聚集之后。α-Syn 是路易体的主要成分。然而，缺乏关于异常 α-syn 聚集扩散的研究，该聚集导致对大脑结构和功能的特定损害。在本研究中，全长人 α-syn 原纤维被注射到大鼠的内侧前脑束中，实验终点为 6 个月。进行组织学分析，观察内源性α-syn异常聚集和神经纤维质量的病理进展。使用基于体素的形态测量 (VBM) 定量分析灰质和白质完整性的变化。在 6 个月期间观察到行为变化。组织学分析显示实验大鼠纹状体中多巴胺转运蛋白水平降低；广泛的异常内源性 α-syn 积累；实验组神经纤维受损、稀疏、紊乱。VBM显示，术后6个月，实验组双侧前边缘、双侧下边缘、右侧海马、右侧皮质体积减少，而与对照组相比，实验组丘脑体积增加。边缘系统和丘脑纤维结构的损伤可能发生在帕金森病的早期阶段。广泛的异常内源性 α-syn 积累；实验组神经纤维受损、稀疏、紊乱。VBM显示，术后6个月，实验组双侧前边缘、双侧下边缘、右侧海马、右侧皮质体积减少，而与对照组相比，实验组丘脑体积增加。边缘系统和丘脑纤维结构的损伤可能发生在帕金森病的早期阶段。广泛的异常内源性 α-syn 积累；实验组神经纤维受损、稀疏、紊乱。VBM显示，术后6个月，实验组双侧前边缘、双侧下边缘、右侧海马、右侧皮质体积减少，而与对照组相比，实验组丘脑体积增加。边缘系统和丘脑纤维结构的损伤可能发生在帕金森病的早期阶段。