Aged hippocampal single‐cell atlas screening unveils disrupted neuroglial system in postoperative cognitive impairment

作者：Zizheng Suo, Ting Xiao, Yinyin Qu, Yuxiang Zheng, Wenjie Xu, Bowen Zhou, Jing Yang, Jie Yu, Hui Zheng, Cheng Ni · 发表于：Aging Cell · 年份：2024 · DOI：10.1111/acel.14406 · 被引用次数：14 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Intensive Care Unit Cognitive Disorders、Single-cell and spatial transcriptomics

Glia-neuron interaction is a crucial feature in aged hippocampus during the occurrence of postoperative cognitive impairment. However, the regulatory effects of microglia, astrocytes, and oligodendrocytes in this glia-neuron interaction, the potential mechanisms and gene targets are still to be elucidated. Here, single-cell RNA sequencing was performed to detect the perioperative genomic expression characteristics of neuroglial system in the hippocampus of aged mice, and to investigate the potential cross-cellular mechanisms and valuable treatment options for glia-neuron interaction-related cognitive impairment. We found that postoperative neurons and glia cells exhibited protein dysmetabolism and mitochondrial electron misrouting. Impaired autophagy and circadian rhythm worsened microglia activation/neuroinflammation, and exacerbated these metabolic alterations. Reactive microglia also aggravated astrocyte and oligodendrocyte cytotoxicity through the PGD2/DP and complement pathways, altering glutamate level and synaptic function via the "tripartite synapses" model, and affecting neuronal myelination. Ligand-receptor communication also indicated these synaptic and axonal dysfunctions via enhanced MDK and PTN pathways. Additionally, we found that anesthetic dexmedetomidine hold therapeutic potential within the disrupted neuroglial system. It enhanced neuronal metabolic rebalance (Atf3-related) and reduced neuroinflammation from a multicellular perspective, therefore improving ...