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

Cells

Andrea Cabrera-Pastor¹  Carmina Montoliu¹  Vicente Felipo²  Paula Izquierdo-Altarejos²  Hernan Gonzalez-King³ 

[1] Health Research Institute INCLIVA, 46010 Valencia, Spain;Laboratory of Neurobiology, Príncipe Felipe Research Center, 46012 Valencia, Spain;Regenerative Medicine and Heart Transplantation Unit, Health Research Institute La Fe, 46026 Valencia, Spain;

关键词: hepatic encephalopathy;    tnfα;    tnfα receptor tnfr1;    glial activation;   

DOI  :  10.3390/cells9030572

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown