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Hepatic Encephalopathy and Astrocyte Senescence
Boris Görg1, Ayşe Karababa1, Dieter Häussinger1
1Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Düsseldorf, Germany.
Journal of Clinical and Experimental Hepatology
|October 11, 2018
Summary
Persistent cognitive impairment in hepatic encephalopathy (HE) may stem from astrocyte senescence, a process linked to oxidative stress. This cellular aging in astrocytes could explain irreversible neurological decline in liver cirrhosis patients with HE.
Area of Science:
- Neuroscience
- Hepatology
- Cell Biology
Background:
- Hepatic Encephalopathy (HE) causes neurological symptoms, and cognitive impairment may persist post-episode in liver cirrhosis.
- Astrocyte senescence, linked to oxidative stress and cognitive decline, is a potential cause for persistent HE-related cognitive impairment.
Purpose of the Study:
- To investigate the role of astrocyte senescence in persistent cognitive impairment in patients with liver cirrhosis and HE.
- To explore the mechanisms of ammonia-induced astrocyte senescence.
Main Methods:
- Analysis of oxidative stress and senescence markers in ammonia-exposed cultured astrocytes.
- Examination of post-mortem brain tissue from liver cirrhosis patients with and without HE.
Main Results:
- Surrogate markers for oxidative stress and senescence were elevated in ammonia-exposed astrocytes and in HE patient brain tissue.
- Ammonia-induced astrocyte senescence involves ROS formation, p53 activation, and cell cycle inhibitors (p21, GADD45α).
- ROS-induced microRNA changes and HO1 upregulation were implicated in ammonia-induced astrocyte proliferation inhibition.
Conclusions:
- Astrocyte senescence is a potential contributor to persistent cognitive impairment in hepatic encephalopathy.
- Ammonia exposure triggers senescence pathways in astrocytes, involving oxidative stress and specific molecular mechanisms.
- Further research is needed to clarify the sequence of events and functional impact of astrocyte senescence in HE.
Keywords:
ARE, Antioxidant Response ElementsBDNF, Brain-Derived Neurotrophic FactorEph, EphrineEphR, Ephrine ReceptorGADD45α, Growth Arrest and DNA Damage Inducible 45αGS, Glutamine SynthetaseHE, Hepatic EncephalopathyHO1, Heme Oxygenase 1LOLA, l-Ornithine-l-AspartateMAP, Mitogen Activated Protein KinasesNAPDH, Reduced Form of Nicotinamide Adenine Dinucleotide PhosphateNox, NADPH OxidaseNrf2, Nuclear Factor-Like 2PBR, Peripheral-Type Benzodiazepine ReceptorPTN, Protein Tyrosine NitrationRNOS, Reactive Nitrogen and Oxygen SpeciesROS, Reactive Oxygen SpeciesSA-β-Gal, Senescence-Associated β-d-GalactosidaseTSP, TrombospondinTrkBT, Truncated Tyrosine Receptor Kinase BZnPP, Zinc Protoporphyrinammoniaastrocytesheme oxygenase 1hepatic encephalopathymPT, Mitochondrial Permeability TransitionmiRNAsnNOS, Neuronal-Type Nitric-Oxide Synthaseoxidative stress
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