Abstract：
The hippocampus is an important part of the limbic system in the human brain that has essential roles in spatial navigation and cognitive functions. It is still unknown how gene expression changes in single-cell in different spatial locations of the hippocampus of Parkinson\'s disease. The purpose of this study was to analyze the gene expression features of single cells in different spatial locations of mouse hippocampus, and to explore the effects of gene expression regulation on learning and memory mechanisms. Here, we obtained 74 single-cell samples from different spatial locations in a mouse hippocampus through microdissection technology, and used single-cell RNA-sequencing and spatial transcriptome sequencing to visualize and quantify the single-cell transcriptome features of tissue sections. The results of differential expression analysis showed that the expression of Sv2b, Neurod6, Grp and Stk32b genes in a hippocampus single cell at different locations was significantly different, and the marker genes of CA1, CA3 and DG subregions were identified. The results of gene function enrichment analysis showed that the up-regulated differentially expressed genes Tubb2a, Eno1, Atp2b1, Plk2, Map4, Pex5l, Fibcd1 and Pdzd2 were mainly involved in neuron to neuron synapse, vesicle-mediated transport in synapse, calcium signaling pathway and neurodegenerative disease pathways, thus affecting learning and memory function. It revealed the transcriptome profile and heterogeneity of spatially located cells in the hippocampus of PD for the first time, and demonstrated that the impaired learning and memory ability of PD was affected by the synergistic effect of CA1 and CA3 subregions neuron genes. These results are crucial for understanding the pathological mechanism of the Parkinson\'s disease and making precise treatment plans.
摘要：
海马是人脑边缘系统的重要组成部分，在空间导航和认知功能中起着重要作用。目前尚不清楚帕金森病海马不同空间位置的单细胞基因表达如何变化。本研究的目的是分析小鼠海马不同空间位置的单个细胞的基因表达特征,并探讨基因表达调控对学习记忆机制的影响。这里,我们通过显微解剖技术从小鼠海马的不同空间位置获得了74个单细胞样本，并使用单细胞RNA测序和空间转录组测序来可视化和量化组织切片的单细胞转录组特征。差异表达分析结果显示，Sv2b的表达，Neurod6、Grp和Stk32b基因在海马单个细胞的不同位置存在显著差异，并鉴定了CA1，CA3和DG亚区的标记基因。基因功能富集分析结果表明,上调的差异表达基因Tubb2a,Eno1,Atp2b1,Plk2,Map4,Pex5l,Fibcd1和Pdzd2主要参与神经元到神经元突触，囊泡介导的突触运输，钙信号通路和神经退行性疾病通路，从而影响学习和记忆功能。它首次揭示了PD海马中空间定位细胞的转录组特征和异质性，并证明PD的学习和记忆能力受损受到CA1和CA3亚区神经元基因协同作用的影响。这些结果对于理解帕金森病的病理机制和制定精确的治疗方案至关重要。
