副干酪乳杆菌的细胞外囊泡可改善高氨血症大鼠的神经炎症、γ-氨基丁酸神经传递和运动不协调。

Extracellular vesicles from L. paracasei improve neuroinflammation, GABA neurotransmission and motor incoordination in hyperammonemic rats.

作者信息

Arenas Yaiza M, Pérez-Martinez Gaspar, Montoliu Carmina, Llansola Marta, Felipo Vicente

机构信息

Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain; Departamento de Patología, Facultad de Medicina, Universidad Valencia, Valencia, Spain; INCLIVA Instituto de Investigación Sanitaria, Valencia, Spain; Laboratory of Lactic Acid Bacteria and Probiotics, Department of Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos (C.S.I.C.), Valencia, Spain.

Laboratory of Lactic Acid Bacteria and Probiotics, Department of Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos (C.S.I.C.), Valencia, Spain.

出版信息

Brain Behav Immun. 2025 Jan;123:556-570. doi: 10.1016/j.bbi.2024.10.002. Epub 2024 Oct 9.

DOI:10.1016/j.bbi.2024.10.002

PMID:39384052

Abstract

Patients with liver cirrhosis may show minimal hepatic encephalopathy (MHE) with motor incoordination and cognitive impairment that reduce life quality and span. Motor incoordination is due to neuroinflammation and enhanced GABAergic neurotransmission in cerebellum. Recent reports support that probiotics, including L. casei, may improve cognitive function in different pathologies and MHE in cirrhotic patients. Extracellular vesicles (EV) are small cell-derived membrane vesicles that carry bioactive molecules released from cells, including bacteria. We hypothesized that EV from Lacticaseibacillus paracasei (LC-EV) could improve neuroinflammation, GABAergic neurotransmission and motor function in MHE. We show that LC-EV treatment reverses glial activation and neuroinflammation in cerebellum and restore motor coordination in hyperammonemic rats. Moreover, ex vivo treatment of cerebellar slices from hyperammonemic rats with LC-EV also reverses glial activation and neuroinflammation, and the enhancement of the TNFR1-S1PR2-BDNF-TrkB and TNFR1-TrkB-pAKT-NFκB-glutaminase-GAT3 pathways and of GABAergic neurotransmission. The results reported support that LC-EV may be used as a therapeutic tool to improve motor incoordination in patients with MHE.

摘要

肝硬化患者可能会出现轻微肝性脑病（MHE），伴有运动不协调和认知障碍，这会降低生活质量和缩短寿命。运动不协调是由于神经炎症以及小脑内GABA能神经传递增强所致。最近的报告支持，包括干酪乳杆菌在内的益生菌可能改善不同病理状态下的认知功能以及肝硬化患者的轻微肝性脑病。细胞外囊泡（EV）是源自细胞的小膜囊泡，携带细胞释放的生物活性分子，包括细菌释放的生物活性分子。我们假设副干酪乳杆菌来源的细胞外囊泡（LC-EV）可以改善轻微肝性脑病中的神经炎症、GABA能神经传递和运动功能。我们发现，LC-EV治疗可逆转高氨血症大鼠小脑的胶质细胞活化和神经炎症，并恢复其运动协调性。此外，用LC-EV对高氨血症大鼠的小脑切片进行离体处理，也可逆转胶质细胞活化和神经炎症，以及TNFR1-S1PR2-BDNF-TrkB和TNFR1-TrkB-pAKT-NFκB-谷氨酰胺酶-GAT3信号通路的增强和GABA能神经传递。报告结果支持LC-EV可作为改善轻微肝性脑病患者运动不协调的治疗工具。