Effects of cholestasis and hyperammonemia on dendritic spine density and turnover in rat hippocampal neurons.

Autor: Giovannoni L; Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Geneva, Switzerland. lauriannegiovannoni@orange.fr.; Department of Basic Neurosciences, University of Geneva Medical School, Geneva, Switzerland. lauriannegiovannoni@orange.fr., Pierzchala K; CIBM Center for Biomedical Imaging, Geneva, Switzerland.; Animal Imaging and Technology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., De Roo M; Department of Basic Neurosciences, University of Geneva Medical School, Geneva, Switzerland.; Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University Hospitals of Geneva, Geneva, Switzerland., Braissant O; Service of Clinical Chemistry, University of Lausanne and University Hospital of Lausanne, Lausanne, Switzerland., Bruce S; Service of Clinical Chemistry, University of Lausanne and University Hospital of Lausanne, Lausanne, Switzerland., McLin VA; Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Geneva, Switzerland., Vutskits L; Department of Basic Neurosciences, University of Geneva Medical School, Geneva, Switzerland.; Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University Hospitals of Geneva, Geneva, Switzerland.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Dec 01; Vol. 14 (1), pp. 29841. Date of Electronic Publication: 2024 Dec 01.
DOI: 10.1038/s41598-024-80871-8
Abstrakt: Adults and children with cholestatic liver disease are at risk for type C hepatic encephalopathy (HE) and may present lifelong neurocognitive impairment. While the underlying cellular and molecular mechanisms are still incompletely understood, ammonium and bile acids (BAs) seem to play a key role in this pathology, by crossing the blood-brain-barrier and modifying neuronal homeostasis and synaptic plasticity. This experimental study aimed to investigate the effects of ammonium and BAs on dendritic spines of rat hippocampal CA1 neurons. Taking advantage of the bile duct ligated (BDL) in vivo rat model and a hippocampal organotypic rat ex vivo slice model, we analyzed dendritic spine density in both models and spine turnover ex vivo. BDL rats showed decreased dendritic spine densities after 8 weeks, paralleled with increased concentrations of blood ammonium. In organotypic hippocampal slices, exposure to ammonium, tauro-α-muricholic and taurocholic acid induced a decrease in dendritic spine density during the first 3 days, followed by an increase in dendritic spinogenesis during days 4-5, resulting in an increased number of dendritic spines. These observations provide new insights into the effects of ammonium and BAs on dendritic spines and consequently synaptic plasticity in chronic cholestatic liver disease.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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