A mitochondrial-derived peptide MOTS-c contributes to the protective effect against brain injury associated with LPS-induced sepsis by strengthening the blood-brain barrier's ultrastructure.

Authors

Yuanyuan Bai, Haiyan Wu, Xu Wang, Yang Guo, Bingqing Gong, Beibei Dong, Yonghao Yu

Published in

The International journal of neuroscience. Pages 1-16. Aug 03, 2025. Epub Aug 03, 2025.

Abstract

Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis, increasing short-term and long-term mortality. It involves neuroinflammation, neuronal damage, and blood-brain barrier (BBB) disruption. MOTS-c, a mitochondrion-derived peptide, exerts neuroprotective effects by modulating inflammatory responses and cellular functions. This study explored the protective effects of MOTS-c against brain injury in mice with LPS-induced sepsis.
A mouse model of sepsis was established via intraperitoneal injection of LPS. The mice were divided into four groups: Control, Control + MOTS-c, LPS, and LPS + MOTS-c groups. The mice in the latter two groups received MOTS-c (20 mg/kg) four hours before model establishment. Survival rates and the murine sepsis score (MSS) were recorded. H&E staining, ELISA, Evans blue staining, brain water content detremination, immunofluorescence staining, western blotting, and qPCR were performed to assess brain tissue damage, inflammation, BBB permeability, and BBB-related protein expression.
MOTS-c treatment increased the survival rate, decreased the MSS score, alleviated brain tissue damage, downregulated the expression of inflammatory factors, reversed the increase in BBB permeability, upregulated the expression of BBB-related proteins and CD31/PDGFRβ, decreased the expression of GFAP/Iba-1/MMP-9, and increased the expression of neurotrophic factors in septic mice.
MOTS-c effectively reduced mortality rates and the MSS, attenuated neuroinflammatory responses, mitigated increase in BBB permeability, promoted neurotrophic factor production, and protecting against brain injury in mice with LPS-induced sepsis.

PMID:
40753494
Bibliographic data and abstract were imported from PubMed on 03 Aug 2025.

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