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. 2024 Aug 8;10(16):e35936.
doi: 10.1016/j.heliyon.2024.e35936. eCollection 2024 Aug 30.

Alternation of gene expression in brain-derived exosomes after cerebral ischemic preconditioning in mice

He Li  1   2 , Xiaoxi Zhang  2 , Hongye Xu  2 , Hanchen Liu  2 , Yongxin Zhang  2 , Lei Zhang  2 , Yu Zhou  2 , Yongwei Zhang  2 , Jianmin Liu  2 , Mei Jing  1 , Ping Zhang  2   3 , Pengfei Yang  2
Affiliations

Alternation of gene expression in brain-derived exosomes after cerebral ischemic preconditioning in mice

He Li et al. Heliyon. .

Abstract

Aims: Cerebral ischemic preconditioning is a neuroprotective therapy against cerebral ischemia and ischemia-reperfusion injury. This study aims to demonstrate the alternation of gene expression in exosomes from brain tissue of mice after ischemic preconditioning and their potential functions.

Methods: Ten mice were divided into the sham and the cerebral ischemic preconditioning groups. Their brain tissues were harvested, from which the exosomes were extracted. The characteristics and protective effects of exosomes were evaluated. Whole transcriptome sequencing was used to demonstrate the gene expression discrepancy between the exosomes from the two groups of mice brains. Volcano graphs and heatmaps were used to picture the difference in expression quantity of mRNA, lncRNA, and circRNA. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to demonstrate the functions of differentially expressed RNAs.

Results: Exosomes were successfully extracted, and those from the cerebral ischemic preconditioning group had better protective effects on cells that received oxygen-glucose deprivation and restoration injury. A total of 306 mRNAs and 374 lncRNAs were significantly upregulated, and 320 mRNAs and 405 lncRNAs were significantly downregulated in the preconditioning group. No circRNAs were differentially expressed between the two groups. GO and KEGG pathway analysis indicated that the functions of differentially expressed RNAs were related to both neural protective and injurious effects.

Conclusion: The brain-derived exosomes may participate in the neuroprotective effect of cerebral ischemic preconditioning. Thorough research is necessary to investigate exosome functions derived from the ischemic preconditioned brain.

Keywords: Cerebral ischemia-reperfusion injury; Cerebral ischemic preconditioning; Exosomes; Neuroprotection; Whole transcriptome sequencing.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Pengfei Yang reports financial support was provided by Stroke Prevention and Treatment Project of the National Health Commission. Pengfei Yang reports financial support was provided by Science and Technology Commission of Shanghai Municipality. He Li reports financial support was provided by Naval Medical University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
(A) Workflow of exosome extraction and the WTS. (B) Western blot analysis of exosomal markers. (C) NTA of the exosomes. (D) TEM observation of the exosomes. (E) Relative viability of each cell line. (F and G) TUNEL staining in each cell group. DAPI-positive and TUNEL-positive cells were detected using 470 nm and 364 nm excitation lasers, respectively. (H) Relative ROS levels in each cell group. (C: Control; C + PBS: Control + PBS; C + SE: Control + exosomes from the Sham group mice; C + IPCE: Control + exosomes from the CIPC group mice; O: OGD/R; O + PBS: OGD/R + PBS; O + SE: OGD/R + exosomes from the Sham group mice; O + IPCE: OGD/R+ exosomes from the CIPC group mice; *, #, $, and! represented p < 0.05 compared to the C, O, O + PBS, and O + SE groups.)
Fig. 2
Fig. 2
(A) Heatmap of differentially expressed mRNAs between exosomes from the Sham and the CIPC groups. (B) Volcano graph of differentially expressed mRNAs between exosomes from the Sham and the CIPC groups. (C–E) Bar plots of GO analysis of the upregulated mRNAs. (F) Dot plot of KEGG pathway analysis of the upregulated mRNAs.
Fig. 3
Fig. 3
(A–C) Bar plots of GO analysis of downregulated mRNAs. (D) Dot plot of KEGG pathway analysis of the downregulated mRNAs.
Fig. 4
Fig. 4
(A) Heatmap of differentially expressed lncRNAs between exosomes from the Sham and the CIPC groups. (B) Volcano graph of differentially expressed lncRNAs between exosomes from the Sham and the CIPC groups. (C–E) Bar plots of GO analysis of the target mRNAs of the upregulated lncRNAs. (F) Dot plot of KEGG pathway analysis of target mRNAs of upregulated lncRNAs.
Fig. 5
Fig. 5
(A–C) Bar plots of GO analysis of the target mRNAs of the downregulated lncRNAs. (D) Dot plot of KEGG pathway analysis of target mRNAs of downregulated lncRNAs.
Fig. 6
Fig. 6
This figure shows the effective components of CIPC-induced exosomes and the directions for future research.
See this image and copyright information in PMC

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