Giovannoni Laurianne, Pierzchala Katarzyna, De Roo Mathias, Braissant Olivier, Bruce Stephen, McLin Valérie Anne, Vutskits Laszlo
Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Geneva, Switzerland.
Department of Basic Neurosciences, University of Geneva Medical School, Geneva, Switzerland.
Sci Rep. 2024 Dec 1;14(1):29841. doi: 10.1038/s41598-024-80871-8.
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.
患有胆汁淤积性肝病的成人和儿童有患C型肝性脑病（HE）的风险，可能会出现终身神经认知障碍。虽然其潜在的细胞和分子机制仍未完全了解，但铵和胆汁酸（BAs）似乎通过穿过血脑屏障并改变神经元内环境稳定和突触可塑性，在这种病理过程中发挥关键作用。本实验研究旨在探讨铵和BAs对大鼠海马CA1神经元树突棘的影响。利用体内胆管结扎（BDL）大鼠模型和体外海马器官型大鼠脑片模型，我们分析了两种模型中的树突棘密度以及体外的树突棘更新情况。BDL大鼠在8周后树突棘密度降低，同时血铵浓度升高。在器官型海马脑片中，暴露于铵、牛磺-α-鼠胆酸和牛磺胆酸在第1至3天导致树突棘密度降低，随后在第4至5天树突棘生成增加，导致树突棘数量增加。这些观察结果为铵和BAs对树突棘的影响以及慢性胆汁淤积性肝病中突触可塑性的影响提供了新的见解。
