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RESEARCH PRODUCT
Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats.
Carmina MontoliuVicente FelinoPaula Izquierdo‐altarejosAndrea Cabrera-pastorHernan Gonzalez-kingsubject
MaleCerebellumtnfαhepatic encephalopathyArticleExtracellular VesiclesImmune systemWestern blotmedicineAnimalsHumansHyperammonemiaRats WistarReceptorlcsh:QH301-705.5NeuroinflammationInflammationMicrogliamedicine.diagnostic_testbusiness.industryTumor Necrosis Factor-alphaHyperammonemiaGeneral Medicinetnfα receptor tnfr1medicine.diseaseRatsMotor Skills DisordersDisease Models Animalmedicine.anatomical_structurelcsh:Biology (General)glial activationTumor necrosis factor alphaNervous System DiseasesTNF alpha receptor TNFR1businessNeuroscienceTNF alphadescription
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-1b, TNF&alpha
year | journal | country | edition | language |
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2020-02-01 |