Single-Cell Insights Into Cellular Response in Abdominal Aortic Occlusion-Induced Hippocampal Injury
Changhong Ren1, Ling Kui2, Jun Xu1
1Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Center of Stroke, Beijing Institute of Brain Disorder, Capital Medical University, Beijing, China.
Insights
Abdominal aorta occlusion (AAO) causes hippocampal injury. Single-cell analysis reveals increased astrocytes and oligodendrocyte precursor cells, with altered gene expression and cellular functions, offering therapeutic targets.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Ischemia-reperfusion injury to the abdominal aorta can damage distant organs, including the brain.
- Cellular heterogeneity in affected tissues complicates understanding injury mechanisms.
- The cell-type-specific molecular pathology in the hippocampus following ischemia is not well understood.
Purpose of the Study:
- To investigate the single-cell transcriptome in the hippocampus of mice subjected to abdominal aorta occlusion (AAO).
- To identify cell type-specific molecular alterations and their functional implications in AAO-induced hippocampal injury.
Main Methods:
- A mouse model of abdominal aorta occlusion (AAO) was established, with animals divided into Sham and Ischemia/Reperfusion (I/R) groups.
- Hippocampal tissues were analyzed using single-cell RNA sequencing and histological methods.
- Neurological function was assessed via behavioral tests over 28 days post-surgery.
Main Results:
- AAO injury led to increased proportions of astrocytes and oligodendrocyte precursor cells (OPCs) (p < 0.05).
- Astrocytes displayed unique gene expression related to neurogenesis and mRNA processing, with five distinct subtypes emerging.
- Microglia activation and altered metabolic pathways (epithelial cell oxidative phosphorylation PPI module) indicated inflammatory and metabolic changes.
Conclusions:
- Single-cell RNA sequencing provided insights into transcriptional changes in the hippocampus following AAO injury.
- The study elucidates the hippocampal response to AAO, identifying potential therapeutic targets for intervention.
Objective:
Ischemia-reperfusion of the abdominal aorta often results in damage to distant organs, such as the heart and brain. This cellular heterogeneity within affected tissues complicates the roles of specific cell subsets in abdominal aorta occlusion model (AAO) injury. However, cell type-specific molecular pathology in the hippocampus after ischemia is poorly understood.
Aims:
In this study, we adopted a mouse AAO to investigate the single-cell transcriptome in the hippocampi in AAO mice.
Methods:
Male C57BL/6 mice (8 weeks old) were used to create an AAO model, with animals divided into Sham and I/R groups. The I/R group was subjected to 2 h of ischemia followed by 24 h of reperfusion, after which hippocampal tissues were collected for single-cell RNA sequencing and histological analysis. Behavioral tests, including the Rotarod, Y-maze, and new object recognition tests, were performed daily for 28 days post-surgery to evaluate neurological function. A total of 62,624 cells were corresponding 7 cell types with neuronal, glial, and vascular lineages. We next analyzed cell-specific gene alterations in AAO mice and the function of these cell-specific Genes.
Results:
AAO injury upregulated astrocyte and oligodendrocyte precursor cell (OPC) proportions (p-value < 0.05). Astrocytes showed unique gene expression related to neurogenesis and mRNA processing. Five distinct astrocyte subtypes emerged post-injury. OPCs exhibited enhanced synapse organization. Microglia activation and the elevated expression level of the epithelial cell oxidative phosphorylation protein-protein interaction (PPI) module indicate an inflammatory response and metabolic changes in response to AAO injury.
Conclusions:
Our scRNA-seq analysis provides insights into transcriptional changes at the single-cell level in response to AAO-induced hippocampal injury. This study illustrates how the hippocampal region responds to such injury and identifies potential therapeutic targets for intervention, thereby paving the way for future research and treatment strategies.
