Loss of monocarboxylate transporter 1 aggravates white matter injury after experimental subarachnoid hemorrhage in rats

Abstract

Monocarboxylic acid transporter 1 (MCT1) maintains axonal function by transferring lactic acid from oligodendrocytes to axons. Subarachnoid hemorrhage (SAH) induces white matter injury, but the involvement of MCT1 is unclear. In this study, the SAH model of adult male Sprague-Dawley rats was used to explore the role of MCT1 in white matter injury after SAH. At 48 h after SAH, oligodendrocyte MCT1 was significantly reduced, and the exogenous overexpression of MCT1 significantly improved white matter integrity and long-term cognitive function. Motor training after SAH significantly increased the number of ITPR2⁺SOX10⁺ oligodendrocytes and upregulated the level of MCT1, which was positively correlated with the behavioral ability of rats. In addition, miR-29b and miR-124 levels were significantly increased in SAH rats compared with non-SAH rats. Further intervention experiments showed that miR-29b and miR-124 could negatively regulate the level of MCT1. This study confirmed that the loss of MCT1 may be one of the mechanisms of white matter damage after SAH and may be caused by the negative regulation of miR-29b and miR-124. MCT1 may be involved in the neurological improvement of rehabilitation training after SAH.

Keywords

microRNAs / monocarboxylate transporter 1 / motor training / subarachnoid hemorrhage / white matter injury

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Acknowledgements

This work was supported by National Key R&D Program of China (Nos. 2018YFC1312600 and 2018YFC1312601), National Natural Science Foundation of China (Nos. 81830036, 81771254, 81771255, 81873741, and 82071307), China Postdoctoral Science Foundation (No. 2019M651954), Natural Science Foundation of Jiangsu Province (Nos. BK20180204 and 20211552), Suzhou Key Medical Centre (No. Szzx201501), Gusu Health Personnel Training Project (No. GSWS2019030), and Grants from Suzhou Government (No. SYS2019045).

Compliance with ethics guidelines

Xin Wu, Zongqi Wang, Haiying Li, Xueshun Xie, Jiang Wu, Haitao Shen, Xiang Li, Zhong Wang, and Gang Chen declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

Electronic Supplementary Material

ƒSupplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-021-0879-9 and is accessible for authorized users.

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