Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats

Cirrhotic patients may show minimal hepatic encephalopathy (MHE) which impairs life quality and span. There is a need of new safe treatments for MHE. Hyperammonemia is a main contributor to MHE. Hyperammonemic rats reproduce the cognitive impairment present in patients with MHE, which is mediated by...

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Autores: Izquierdo-Altarejos, P, Arenas, YM, Montoliu, C, Pérez-Martínez, G, Llansola, M, Felipo, V
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Centro de Investigación Principe Felipe (CIPF)
Repositorio:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
OAI Identifier:oai:cipf.fundanetsuite.com:p4541
Acceso en línea:https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4541
Access Level:acceso abierto
Palabra clave:Lacticaseibacillus paracasei
Extracellular vesicles
Hepatic encephalopathy
Hyperammonemia
Neuroinflammation
Cognitive impairment
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spelling Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic ratsIzquierdo-Altarejos, PArenas, YMMontoliu, CPérez-Martínez, GLlansola, MFelipo, VLacticaseibacillus paracaseiExtracellular vesiclesHepatic encephalopathyHyperammonemiaNeuroinflammationCognitive impairmentCirrhotic patients may show minimal hepatic encephalopathy (MHE) which impairs life quality and span. There is a need of new safe treatments for MHE. Hyperammonemia is a main contributor to MHE. Hyperammonemic rats reproduce the cognitive impairment present in patients with MHE, which is mediated by neuroinflammation and altered glutamatergic neurotransmission in hippocampus. Probiotics induce positive effects in MHE patients, which could be mediated by bacterial extracellular vesicles (EVs). The aims of this work were to evaluate in hyperammonemic rats: 1) if intravenous administration of EVs from L. paracasei improves memory and learning and 2) reduces neuroinflammation in hippocampus and 3) to study the mechanisms involved using an ex vivo approach. It is shown that intravenous injection of EVs from L. paracasei reverses glial activation in hippocampus and cognitive impairment in hyperammonemic rats. Ex vivo studies in hippocampal slices show that hyperammonemia increases TNF alpha and TNFR1 and S1PR2 membrane expression and activation, leading to increased IL1(3 content and activation of IL-1 receptor and of Src. This increases CCL2 and BDNF and TrkB activation. This leads to increased membrane expression of the NR2B subunit of the NMDA receptor and of the GluA2 subunit of AMPA receptors and reduced membrane expression of the GluA1 subunit, leading to cognitive impairment. EVs from L. paracasei reduce neuroinflammation in hyperammonemic rats and restore the function of the TNF alpha TNFR1-S1PR2-IL-1(3-CCL2-BDNF-TrkB pathway, glutamatergic neurotransmission and cognitive function in rats with hyperammonemia and MHE. This suggests that these EVs could also improve cognitive function in cirrhotic patients with MHE.ELSEVIER GMBH2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4541MICROBIOLOGICAL RESEARCHISSN: 09445013ISSNe: 16180623reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)instname:Centro de Investigación Principe Felipe (CIPF)Inglésinfo:eu-repo/semantics/openAccessoai:cipf.fundanetsuite.com:p45412026-06-17T11:19:47Z
dc.title.none.fl_str_mv Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats
title Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats
spellingShingle Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats
Izquierdo-Altarejos, P
Lacticaseibacillus paracasei
Extracellular vesicles
Hepatic encephalopathy
Hyperammonemia
Neuroinflammation
Cognitive impairment
title_short Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats
title_full Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats
title_fullStr Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats
title_full_unstemmed Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats
title_sort Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats
dc.creator.none.fl_str_mv Izquierdo-Altarejos, P
Arenas, YM
Montoliu, C
Pérez-Martínez, G
Llansola, M
Felipo, V
author Izquierdo-Altarejos, P
author_facet Izquierdo-Altarejos, P
Arenas, YM
Montoliu, C
Pérez-Martínez, G
Llansola, M
Felipo, V
author_role author
author2 Arenas, YM
Montoliu, C
Pérez-Martínez, G
Llansola, M
Felipo, V
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Lacticaseibacillus paracasei
Extracellular vesicles
Hepatic encephalopathy
Hyperammonemia
Neuroinflammation
Cognitive impairment
topic Lacticaseibacillus paracasei
Extracellular vesicles
Hepatic encephalopathy
Hyperammonemia
Neuroinflammation
Cognitive impairment
description Cirrhotic patients may show minimal hepatic encephalopathy (MHE) which impairs life quality and span. There is a need of new safe treatments for MHE. Hyperammonemia is a main contributor to MHE. Hyperammonemic rats reproduce the cognitive impairment present in patients with MHE, which is mediated by neuroinflammation and altered glutamatergic neurotransmission in hippocampus. Probiotics induce positive effects in MHE patients, which could be mediated by bacterial extracellular vesicles (EVs). The aims of this work were to evaluate in hyperammonemic rats: 1) if intravenous administration of EVs from L. paracasei improves memory and learning and 2) reduces neuroinflammation in hippocampus and 3) to study the mechanisms involved using an ex vivo approach. It is shown that intravenous injection of EVs from L. paracasei reverses glial activation in hippocampus and cognitive impairment in hyperammonemic rats. Ex vivo studies in hippocampal slices show that hyperammonemia increases TNF alpha and TNFR1 and S1PR2 membrane expression and activation, leading to increased IL1(3 content and activation of IL-1 receptor and of Src. This increases CCL2 and BDNF and TrkB activation. This leads to increased membrane expression of the NR2B subunit of the NMDA receptor and of the GluA2 subunit of AMPA receptors and reduced membrane expression of the GluA1 subunit, leading to cognitive impairment. EVs from L. paracasei reduce neuroinflammation in hyperammonemic rats and restore the function of the TNF alpha TNFR1-S1PR2-IL-1(3-CCL2-BDNF-TrkB pathway, glutamatergic neurotransmission and cognitive function in rats with hyperammonemia and MHE. This suggests that these EVs could also improve cognitive function in cirrhotic patients with MHE.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4541
url https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4541
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER GMBH
publisher.none.fl_str_mv ELSEVIER GMBH
dc.source.none.fl_str_mv MICROBIOLOGICAL RESEARCH
ISSN: 09445013
ISSNe: 16180623
reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
instname:Centro de Investigación Principe Felipe (CIPF)
instname_str Centro de Investigación Principe Felipe (CIPF)
reponame_str r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
collection r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
repository.name.fl_str_mv
repository.mail.fl_str_mv
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