Institute of Neural and Sensory Physiology, Medical Faculty, University of Düsseldorf D-40225 Düsseldorf, Germany.
Arch Biochem Biophys. 2013 Aug 15;536(2):183-8. doi: 10.1016/j.abb.2013.04.008. Epub 2013 Apr 25.
Hepatic encephalopathy (HE)(1) is a common neuropsychiatric complication of both acute and chronic liver disease. Clinical symptoms may include motor disturbances and cognitive dysfunction. Available animal models of HE mimic the deficits in cognitive performance including the impaired ability to learn and memorize information. This review explores the question how HE might affect cognitive functions at molecular levels. Both acute and chronic models of HE constrain the plasticity of glutamatergic neurotransmission. Thus, long-lasting activity-dependent changes in synaptic efficiency, known as long-term potentiation (LTP) and long-term depression (LTD) are significantly impeded. We discuss molecules and signal transduction pathways of LTP and LTD that are targeted by experimental HE, with a focus on ionotropic glutamate receptors of the AMPA-subtype. Finally, a novel strategy of functional proteomic analysis is presented, which, if applied differentially, may provide molecular insight into disease-related dysfunction of membrane protein complexes, i.e. disturbed ionotropic glutamate receptor signaling in HE.
肝性脑病（HE）（1）是急性和慢性肝病的常见神经精神并发症。临床症状可能包括运动障碍和认知功能障碍。现有的 HE 动物模型模拟认知表现的缺陷，包括学习和记忆信息的能力受损。本综述探讨了 HE 如何在分子水平上影响认知功能的问题。急性和慢性 HE 模型均限制了谷氨酸能神经传递的可塑性。因此，突触效率的长时程依赖变化，即长时程增强（LTP）和长时程抑制（LTD），受到显著阻碍。我们讨论了实验性 HE 靶向的 LTP 和 LTD 的分子和信号转导途径，重点是 AMPA 型离子型谷氨酸受体。最后，提出了一种新的功能蛋白质组学分析策略，如果应用得当，可能会为膜蛋白复合物的疾病相关功能障碍提供分子见解，即 HE 中离子型谷氨酸受体信号转导紊乱。
