Hippocampal single-cell atlas screening unveils disrupted neuroglial system in postoperative cognitive impairment
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ABSTRACT:
PROVIDER: PRJNA1113658 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR29089909.fastq.gz | Fastqsanger.gz | |||
| SRR29089910.fastq.gz | Fastqsanger.gz |
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Project description:This study investigates the roles of neurons, microglia, astrocytes, and oligodendrocytes in the pathogenesis of postoperative cognitive impairment, focusing on a dysregulated glia-neuron cycle. We utilized 18-month male C57BL/6 mice to model this condition, conducting single-cell RNA sequencing in the hippocampus to explore the neuroglial interactions and their implications in neuroinflammation, synaptic dysfunction, and myelin loss. This dataset includes transcriptomic profiles aimed at decoding the cellular communication in aged hippocampal cells and assessing the impact of therapeutic interventions on postoperative cognitive decline.
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Project description: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 postoperative cognitive impairment. Together, our study proposes an aged hippocampal cell atlas and provides insights into the role of disrupted glia-neuron cycle in postoperative cognitive impairment. Our findings also elucidate the therapeutic potential and mechanism of dexmedetomidine intervention.
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