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

Autores de CIPF

• 

  Yaiza Arenas Ortiz

  Autor

• Carmina Montoliu Felix

  Autor

• 

  Marta Llansola Gil

  Autor

• 

  Vicente Felipo Orts

  Autor

Participantes ajenos a CIPF

• Pérez-Martinez G

Grupos de Investigación

• Laboratorio de Neurobiología

  

  Jefe/a de Grupo

  Vicente Felipo Orts

• Unidad Mixta CIPF-INCLIVA de Deterioro Neurológico

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-NF?B-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.

Keywords

• Extracellular vesicles, GABAergic neurotransmission, Hepatic encephalopathy, Hyperammonemia, Lacticaseibacillus paracasei, Motor incoordination, Neuroinflammation