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Brain-Derived Exosomal miRNA Profiles upon Experimental SAE Rats and Their Comparison with Peripheral Exosomes

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Abstract

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction secondary to body infection without overt central nervous system infection. Dysregulation of miRNA expression in the transcriptome can spread through RNA transfer in exosomes, providing an early signal of impending neuropathological changes in the brain. Here, we comprehensively analyzed brain-derived exosomal miRNA profiles in SAE rats (n = 3) and controls (n = 3). We further verified the differential expression and correlation of brain tissue, cerebrospinal fluid, and plasma exosomal miRNAs in SAE rats. High-throughput sequencing of brain-derived exosomal miRNAs identified 101 differentially expressed miRNAs, of which 16 were downregulated and 85 were upregulated. Four exosomal miRNAs (miR-127-3p, miR-423-3p, mR-378b, and miR-106-3p) were differentially expressed and correlated in the brain tissue, cerebrospinal fluid, and plasma, revealing the potential use of miRNAs as SAE liquid brain biopsies. Understanding exosomal miRNA profiles in SAE brain tissue and exploring the correlation with peripheral exosomal miRNA can contribute to a comprehensive understanding of miRNA changes in the SAE pathological process and provide the possibility of establishing early diagnostic assays.

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All relevant data for the present study are in the manuscript and Supplementary Information.

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Acknowledgements

We thank the Institute of Cerebrovascular Diseases and Medical Research Center of the Affiliated Hospital of Qingdao University for the platform support.

Funding

This work was supported by the Natural Science Foundation of Shandong Province (ZR2020MH138).

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Q.X., X.Y., R.H., X.P., and X.Z. contributed to the conception and design of the study; Q.X., X.Y., Y.S., and Y.T. performed the experiments and data collection and analyzed the data; Q.X., X.Y., and X.Z. contributed to drafting the text or preparing the figures.

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Correspondence to Rongyao Hou, Xudong Pan or Xiaoyan Zhu.

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Xiao, Q., Yan, X., Sun, Y. et al. Brain-Derived Exosomal miRNA Profiles upon Experimental SAE Rats and Their Comparison with Peripheral Exosomes. Mol Neurobiol 61, 772–782 (2024). https://doi.org/10.1007/s12035-023-03569-4

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