Laboratory of Neuroanatomy, Fondazione Santa Lucia IRCCS, 00143 Rome, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
Int J Mol Sci. 2022 Sep 4;23(17):10126. doi: 10.3390/ijms231710126.
Parkinson's disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein, encoded by the gene. The main neuropathological hallmark of PD is the degeneration of dopaminergic neurons leading to striatal dopamine depletion. Trophic support by a neurotrophin called glial-derived neurotrophic factor (GDNF) is also lacking in PD. We performed immunohistochemical studies to investigate neuropathological changes in the basal ganglia of a rat transgenic model of PD overexpressing alfa-synuclein. We observed that neuronal loss also occurs in the dorsolateral part of the striatum in the advanced stages of the disease. Moreover, along with the degeneration of the medium spiny projection neurons, we found a dramatic loss of parvalbumin interneurons. A marked decrease in GDNF, which is produced by parvalbumin interneurons, was observed in the striatum and in the substantia nigra of these animals. This confirmed the involvement of the striatum in the pathophysiology of PD and the importance of GDNF in maintaining the health of the substantia nigra.
帕金森病（PD）是一种神经退行性疾病，其特征是α-突触核蛋白的积累，该蛋白由 基因编码。PD 的主要神经病理学标志是多巴胺能神经元的退化，导致纹状体多巴胺耗竭。神经胶质衍生的神经营养因子（GDNF）等神经营养因子的营养支持也在 PD 中缺乏。我们进行了免疫组织化学研究，以调查过表达α-突触核蛋白的 PD 大鼠转基因模型基底神经节的神经病理学变化。我们观察到，在疾病的晚期，纹状体的背外侧部分也会发生神经元丢失。此外，随着中型棘突投射神经元的退化，我们发现副甲状腺素中间神经元明显丢失。在这些动物的纹状体和黑质中观察到产生的 GDNF 明显减少。这证实了纹状体参与 PD 的病理生理学，以及 GDNF 在维持黑质健康方面的重要性。
