Dopaminergic neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson’s disease (PD), while those in the dorsal tier and ventral tegmental area are relatively spared. The factors determining why these neurons are more vulnerable than others are still unrevealed. Neuroinflammation and immune cell infiltration have been demonstrated to be a key feature of neurodegeneration in PD. However, the link between selective dopaminergic neuron vulnerability, glial and immune cell response, and vascularization and their interactions has not been deciphered. We aimed to investigate the contribution of glial cell activation and immune cell infiltration in the selective vulnerability of ventral dopaminergic neurons within the midbrain in a non-human primate model of PD. Structural characteristics of the vasculature within specific regions of the midbrain were also evaluated. Parkinsonian monkeys exhibited significant microglial and astroglial activation in the whole midbrain, but no major sub-regional differences were observed. Remarkably, the ventral substantia nigra was found to be typically more vascularized compared to other regions. This feature might play some role in making this region more susceptible to immune cell infiltration under pathological conditions, as greater infiltration of both T- and B- lymphocytes was observed in parkinsonian monkeys. Higher vascular density within the ventral region of the SNc may be a relevant factor for differential vulnerability of dopaminergic neurons in the midbrain. The increased infiltration of T- and B- cells in this region, alongside other molecules or toxins, may also contribute to the susceptibility of dopaminergic neurons in PD.

黑质致密部（SNc）腹侧层的多巴胺能神经元在帕金森病（PD）中显着退化，而背侧和腹侧被盖区的多巴胺能神经元相对幸免。决定这些神经元为何比其他神经元更脆弱的因素仍不清楚。神经炎症和免疫细胞浸润已被证明是帕金森病神经变性的一个关键特征。然而，选择性多巴胺能神经元脆弱性、神经胶质细胞和免疫细胞反应、血管形成及其相互作用之间的联系尚未被阐明。我们的目的是在非人灵长类帕金森病模型中研究胶质细胞激活和免疫细胞浸润对中脑腹侧多巴胺能神经元选择性脆弱性的影响。还评估了中脑特定区域内脉管系统的结构特征。帕金森猴在整个中脑中表现出显着的小胶质细胞和星形胶质细胞激活，但没有观察到主要的亚区域差异。值得注意的是，与其他区域相比，腹侧黑质通常具有更多的血管化。这一特征可能在使该区域在病理条件下更容易受到免疫细胞浸润的影响中发挥一定作用，因为在帕金森病猴中观察到 T 淋巴细胞和 B 淋巴细胞的浸润程度更高。 SNc 腹侧区域内较高的血管密度可能是中脑多巴胺能神经元不同脆弱性的相关因素。该区域 T 细胞和 B 细胞浸润的增加以及其他分子或毒素也可能导致 PD 中多巴胺能神经元的易感性。