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Exosomal LncRNA TM7SF3-AU1 Aggravates White Matter Injury via MiR-702-3p/SARM1 Signaling After Subarachnoid Hemorrhage in Rats

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Abstract

Subarachnoid hemorrhage (SAH) is a devastating disease associated with a high mortality and morbidity. Exosomes have been considered as a potential therapeutic target for SAH. However, the effect of exosomes in SAH remains to be elucidated. In this study, we focused on investigating the effect of plasma exosomal lncRNA TM7SF3-AU1 in white matter injury after SAH. The SAH model was established by means of endovascular perforation. Exosomes were extracted from rat plasma samples. The expression of RNAs in the exosomes was detected by the transcriptomic microarray. Differentially expressed circRNA, lncRNA, and mRNA were obtained. The ceRNA network showed that the lncRNA TM7SF3-AU1 and miR-702-3p were closely associated with SARM1. Knocking down TM7SF3-AU1 promoted the expression of miR-702-3p and suppressed the expression of SARM1, and knocking down TM7SF3-AU1 also attenuated white matter injury after SAH. In addition, knocking down TM7SF3-AU1 improved the neurological deficits in locomotion, anxiety, learning, memory, and electrophysiological activity after SAH. Mechanistically, TM7SF3-AU1 was able to absorb miR-702-3p, which directly bind the SARM1 mRNA. Furthermore, the white matter injury attenuated by knockdown of TM7SF3-AU1 was partially reversed by the miR-702-3p antagomir in SAH rats. Taken together, this study showed that TM7SF3-AU1 acts as a sponge for miR-702-3p, reducing the inhibitory effect of miR-702-3p on SARM1, resulting in increased SARM1 expression and thus leading to white matter injury after SAH. Our study provides new insights into exosome-associated white matter injury. It also highlights TM7SF3-AU1 as a potential therapeutic target for white matter injury after SAH.

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Data Availability

The data that support the findings of the present study are available from the corresponding author upon reasonable request.

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We sincerely thank ** **a

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  1. Zhaosi Zhang
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  2. ** Yan
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  3. Hong Chen
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  4. Guosheng Zhao
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  • Chao Zhou
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  • **aochuan Sun
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    • Contributions

    ZZ and XS conceived and designed the study. ZZ, JY, and HC performed all the experiments. GZ, LL, and XX analyzed the data. ZZ and XS wrote the manuscript. CZ and JY supervised the project. All authors contributed to the article and approved the submitted version.

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    Correspondence to **aochuan Sun.

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    All experiments of animals were approved by Chongqing Medical University Animal Care in accordance with the Guide for the Care and Use of Laboratory Animals by the National Institute of Health.

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    Zhang, Z., Yan, J., Chen, H. et al. Exosomal LncRNA TM7SF3-AU1 Aggravates White Matter Injury via MiR-702-3p/SARM1 Signaling After Subarachnoid Hemorrhage in Rats. Mol Neurobiol 61, 4783–4803 (2024). https://doi.org/10.1007/s12035-023-03811-z

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