Hepatic encephalopathy is linked to alterations of autophagic flux in astrocytes.

ABSTRACT:

Background

Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome caused by various types of liver failure resulting in hyperammonemia-induced dysfunction of astrocytes. It is unclear whether autophagy, an important pro-survival pathway, is altered in the brains of ammonia-intoxicated animals as well as in HE patients.

Methods

Using primary rat astrocytes, a co-culture model of primary mouse astrocytes and neurons, an in vivo rat HE model, and post mortem brain samples of liver cirrhosis patients with HE we analyzed whether and how hyperammonemia modulates autophagy.

Findings

We show that autophagic flux is efficiently inhibited after administration of ammonia in astrocytes. This occurs in a fast, reversible, time-, dose-, and ROS-dependent manner and is me

SUBMITTER: Lu K 

PROVIDER: S-EPMC6838440 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature