Fitzgerald Julia C, Sun Ying, Reinecke Frederek, Bauer Elisabeth, Garaschuk Olga, Kahle Philipp J, Pfeiffer Friederike
Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Institute for Physiology, University of Tübingen, Tübingen, Germany.
J Neurochem. 2025 Jan;169(1):e16298. doi: 10.1111/jnc.16298.
Parkinson's disease (PD) is a prevalent neurodegenerative disease caused by the death of dopaminergic neurons within the substantia nigra pars compacta (SNpc) region of the midbrain. Recent genomic and single cell sequencing data identified oligodendrocytes and oligodendrocyte precursor cells (OPCs) to confer genetic risk in PD, but their biological role is unknown. Although SNpc dopaminergic neurons are scarcely or thinly myelinated, there is a gap in the knowledge concerning the physiological interactions between dopaminergic neurons and oligodendroglia. We sought to investigate the distribution of OPCs with regard to the myelination state in the mouse substantia nigra (SN) by high-resolution imaging to provide a morphological assessment of OPC-dopaminergic neuron interactions and quantification of cell numbers across different age groups. OPCs are evenly distributed in the midbrain throughout the lifespan and they physically interact with both the soma and axons of dopaminergic neurons. The presence of OPCs and their interaction with dopaminergic neurons does not correlate with the distribution of myelin. Myelination is sparse in the SNpc, including dopaminergic fibers originating from the SNpc and projecting through the substantia nigra pars reticulata (SNpr). We report that OPCs and dopaminergic neurons exist in a 1:1 ratio in the SNpc, with OPCs accounting for 15%-16% of all cells in the region across all age groups. This description of OPC-dopaminergic neuron interaction in the midbrain provides a first look at their longitudinal distribution in mice, suggesting additional functions of OPCs beyond their differentiation into myelinating oligodendrocytes.
帕金森病（PD）是一种常见的神经退行性疾病，由中脑黑质致密部（SNpc）区域的多巴胺能神经元死亡引起。最近的基因组和单细胞测序数据表明，少突胶质细胞和少突胶质前体细胞（OPC）在帕金森病中具有遗传风险，但其生物学作用尚不清楚。尽管SNpc多巴胺能神经元的髓鞘形成很少或很薄，但多巴胺能神经元与少突胶质细胞之间生理相互作用的相关知识仍存在空白。我们试图通过高分辨率成像研究小鼠黑质（SN）中OPC在髓鞘形成状态方面的分布，以对OPC与多巴胺能神经元的相互作用进行形态学评估，并对不同年龄组的细胞数量进行量化。OPC在整个生命周期中均匀分布于中脑，并且它们与多巴胺能神经元的胞体和轴突都存在物理相互作用。OPC的存在及其与多巴胺能神经元的相互作用与髓鞘的分布无关。SNpc中的髓鞘形成很少，包括源自SNpc并穿过黑质网状部（SNpr）的多巴胺能纤维。我们报告称，在SNpc中，OPC与多巴胺能神经元的比例为1:1，在所有年龄组中，OPC占该区域所有细胞的15%-16%。对中脑OPC与多巴胺能神经元相互作用的这一描述首次展示了它们在小鼠中的纵向分布，表明OPC除了分化为髓鞘形成少突胶质细胞之外还具有其他功能。
