Abstract
Transient receptor potential mucolipin-1 (TRPML1) is the most abundantly and widely expressed channel protein in the TRP family. While numerous studies have been conducted involving many aspects of TRPML1, such as its role in cell biology, oncology, and neurodegenerative diseases, there are limited reports about what role it plays in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Here we examined the function of TRPML1 in ICH-induced SBI. The caudal arterial blood of rats was injected into the caudate nucleus of basal ganglia to establish an experimental ICH model. We observed that lentivirus downregulated the expression level of TRPML1 and chemical agonist promoted the enzyme activity of TRPML1. The results indicated that the protein levels of TRPML1 in brain tissues increased 24 h after ICH. These results suggested that downregulated TRPML1 could significantly reduce inflammatory cytokines, and ICH induced the production of LDH and ROS. Furthermore, TRPML1 knockout relieved ICH-induced neuronal cell death and degeneration, and declines in learning and memory after ICH could be improved by downregulating the expression of TRPML1. In addition, chemical agonist-expressed TRPML1 showed the opposite effect and exacerbated SBI after ICH. In summary, this study demonstrated that TRPML1 contributed to brain injury after ICH, and downregulating TRPML1 could improve ICH-induced SBI, suggesting a potential target for ICH therapy.
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Data availability
The datasets generated and/or analyzed during the current study are not publicly available due to the confidential policy of our hospital but are available from the corresponding author on reasonable request.
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The National Natural Science Foundation of China (No.81830036), the Natural Science Foundation of Jiangsu Province under Grant (No. BK20220096), the Suzhou Science and Technology (No. SS2019056), Jiangsu Commission of Health (No. K2019001), Suzhou Key Medical Center (No. Szzx201501), and Suzhou Government (No. SYS2019045).
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Shi, J., Li, X., Ding, J. et al. Transient Receptor Potential Mucolipin-1 Participates in Intracerebral Hemorrhage-Induced Secondary Brain Injury by Inducing Neuroinflammation and Neuronal Cell Death. Neuromol Med 25, 272–285 (2023). https://doi.org/10.1007/s12017-023-08734-5
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DOI: https://doi.org/10.1007/s12017-023-08734-5