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Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats

Fecha de publicación:

Autores de CIPF

Grupos de Investigación

Abstract

Minimal hepatic encephalopathy is associated with changes in the peripheral immune system which are transferred to the brain, leading to neuroinflammation and thus to cognitive and motor impairment. Mechanisms by which changes in the immune system induce cerebral alterations remain unclear. Extracellular vesicles (EVs) seem to play a role in this process in certain pathologies. The aim of this work was to assess whether EVs play a role in the induction of neuroinflammation in cerebellum and motor incoordination by chronic hyperammonemia. We characterized the differences in protein cargo of EVs from plasma of hyperammonemic and control rats by proteomics and Western blot. We assessed whether injection of EVs from hyperammonemic to normal rats induces changes in neuroinflammation in cerebellum and motor incoordination similar to those exhibited by hyperammonemic rats. We found that hyperammonemia increases EVs amount and alters their protein cargo. Differentially expressed proteins are mainly associated with immune system processes. Injected EVs enter Purkinje neurons and microglia. Injection of EVs from hyperammonemic, but not from control rats, induces motor incoordination, which is mediated by neuroinflammation, microglia and astrocytes activation and increased IL-1 beta, TNF alpha, its receptor TNFR1, NF-kappa B in microglia, glutaminase I, and GAT3 in cerebellum. Plasma EVs from hyperammonemic rats carry molecules necessary and sufficient to trigger neuroinflammation in cerebellum and the mechanisms leading to motor incoordination.

Datos de la publicación

ISSN/ISSNe:
2073-4409, 2073-4409

Cells  MDPI

Tipo:
Article
Páginas:
-
PubMed:
32121257

Citas Recibidas en Web of Science: 30

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Keywords

  • hepatic encephalopathy; TNF alpha; TNF alpha receptor TNFR1; glial activation

Campos de Estudio

Proyectos asociados

Bases moleculares de las alteraciones neurológicas (cognitivas y motoras) en hiperamonemia y encefalopatía hepática. Implicaciones terapéuticas

Investigador Principal: VICENTE FELIPO ORTS

MINISTERIO DE ECON. Y COMPET. . 2018

Mecanismos moleculares y cerebrales de las alteraciones cognitivas y motoras en hiperamonemia y encefalopatía hepática. Implicaciones terapeúticas y diagnósticas

Investigador Principal: VICENTE FELIPO ORTS

CONSELLERIA DE EDUCACION . 2018

Identification and modelling of molecular and cellular events of the inmune response associated to the appearence of minimal hepatic encephalopaty in cirrhotic patients

Investigador Principal: VICENTE FELIPO ORTS

FUNDACION RAMON ARECES . 2019

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