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Published on: June 2, 2022
Extracellular vesicles from L. paracasei improve neuroinflammation, GABA neurotransmission and motor incoordination
Yaiza M Arenas1, Gaspar Pérez-Martinez2, Carmina Montoliu3
1Laboratory 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.
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.
Insights
Extracellular vesicles (EV) from Lacticaseibacillus paracasei (LC-EV) show potential in treating minimal hepatic encephalopathy (MHE). LC-EV therapy improved motor coordination and reduced neuroinflammation in MHE rat models.
Area of Science:
- Neuroscience
- Gastroenterology
- Microbiology
Background:
- Minimal hepatic encephalopathy (MHE) in liver cirrhosis patients causes motor and cognitive deficits.
- Neuroinflammation and enhanced GABAergic neurotransmission in the cerebellum contribute to MHE-related motor incoordination.
- Probiotics, like L. casei, and their derived extracellular vesicles (EV) show promise in improving cognitive function and MHE.
Purpose of the Study:
- To investigate the therapeutic potential of extracellular vesicles from Lacticaseibacillus paracasei (LC-EV) in ameliorating neuroinflammation, GABAergic neurotransmission, and motor dysfunction in MHE.
- To explore the underlying molecular mechanisms of LC-EV action in a rat model of MHE.
Main Methods:
- Treatment of hyperammonemic rats, a model for MHE, with LC-EV.
- Ex vivo treatment of cerebellar slices from hyperammonemic rats with LC-EV.
- Assessment of glial activation, neuroinflammation, motor coordination, and specific molecular pathways (e.g., TNFR1-S1PR2-BDNF-TrkB, TNFR1-TrkB-pAKT-NFκB-glutaminase-GAT3).
Main Results:
- LC-EV treatment effectively reversed glial activation and neuroinflammation in the cerebellum of hyperammonemic rats.
- Motor coordination was restored in rats following LC-EV administration.
- Ex vivo experiments confirmed that LC-EVs reduced glial activation and neuroinflammation in cerebellar slices, while also normalizing enhanced GABAergic neurotransmission and specific molecular pathways.
Conclusions:
- Extracellular vesicles derived from Lacticaseibacillus paracasei (LC-EV) demonstrate significant therapeutic potential for MHE.
- LC-EVs can improve motor incoordination by targeting neuroinflammation and GABAergic neurotransmission in the cerebellum.
- LC-EVs represent a promising novel therapeutic strategy for managing motor deficits in patients with MHE.
