Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats
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. Extracel...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/3/572 |
| _version_ | 1797708209508581376 |
|---|---|
| author | Paula Izquierdo-Altarejos Andrea Cabrera-Pastor Hernan Gonzalez-King Carmina Montoliu Vicente Felipo |
| author_facet | Paula Izquierdo-Altarejos Andrea Cabrera-Pastor Hernan Gonzalez-King Carmina Montoliu Vicente Felipo |
| author_sort | Paula Izquierdo-Altarejos |
| collection | DOAJ |
| description | 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-1β, TNFα, its receptor TNFR1, NF-κB 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. |
| first_indexed | 2024-03-12T06:19:02Z |
| format | Article |
| id | doaj.art-b6be7b648d3f4c239e54ec9eeed6c816 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:19:02Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b6be7b648d3f4c239e54ec9eeed6c8162023-09-03T02:22:38ZengMDPI AGCells2073-44092020-02-019357210.3390/cells9030572cells9030572Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control RatsPaula Izquierdo-Altarejos0Andrea Cabrera-Pastor1Hernan Gonzalez-King2Carmina Montoliu3Vicente Felipo4Laboratory of Neurobiology, Príncipe Felipe Research Center, 46012 Valencia, SpainHealth Research Institute INCLIVA, 46010 Valencia, SpainRegenerative Medicine and Heart Transplantation Unit, Health Research Institute La Fe, 46026 Valencia, SpainHealth Research Institute INCLIVA, 46010 Valencia, SpainLaboratory of Neurobiology, Príncipe Felipe Research Center, 46012 Valencia, SpainMinimal 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-1β, TNFα, its receptor TNFR1, NF-κB 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.https://www.mdpi.com/2073-4409/9/3/572hepatic encephalopathytnfαtnfα receptor tnfr1glial activation |
| spellingShingle | Paula Izquierdo-Altarejos Andrea Cabrera-Pastor Hernan Gonzalez-King Carmina Montoliu Vicente Felipo Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats Cells hepatic encephalopathy tnfα tnfα receptor tnfr1 glial activation |
| title | Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats |
| title_full | Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats |
| title_fullStr | Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats |
| title_full_unstemmed | Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats |
| title_short | Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats |
| title_sort | extracellular vesicles from hyperammonemic rats induce neuroinflammation and motor incoordination in control rats |
| topic | hepatic encephalopathy tnfα tnfα receptor tnfr1 glial activation |
| url | https://www.mdpi.com/2073-4409/9/3/572 |
| work_keys_str_mv | AT paulaizquierdoaltarejos extracellularvesiclesfromhyperammonemicratsinduceneuroinflammationandmotorincoordinationincontrolrats AT andreacabrerapastor extracellularvesiclesfromhyperammonemicratsinduceneuroinflammationandmotorincoordinationincontrolrats AT hernangonzalezking extracellularvesiclesfromhyperammonemicratsinduceneuroinflammationandmotorincoordinationincontrolrats AT carminamontoliu extracellularvesiclesfromhyperammonemicratsinduceneuroinflammationandmotorincoordinationincontrolrats AT vicentefelipo extracellularvesiclesfromhyperammonemicratsinduceneuroinflammationandmotorincoordinationincontrolrats |