Monfort Pilar, Erceg Slaven, Piedrafita Blanca, Llansola Marta, Felipo Vicente
Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Avda, Autopista del Saler, 16, 46013, Valencia, Spain.
Eur J Neurosci. 2007 Apr;25(7):2103-11. doi: 10.1111/j.1460-9568.2007.05444.x.
Cognitive function is impaired in patients with liver disease by unknown mechanisms. Long-term potentiation (LTP) in the hippocampus is considered the basis of some forms of learning and memory. The aims of this work were to assess (i) whether chronic liver failure impairs hippocampal LTP; (ii) if this impairment may be due to alterations in glutamatergic neurotransmission, and (iii) if impairment of LTP is associated with reduced learning ability. It is shown that liver failure in Wistar rats induces the following alterations in the hippocampus; (i) alters the phosphorylation of NMDA and AMPA receptors; (ii) reduces the expression of NMDA and AMPA receptors in membranes, (iii) reduces the magnitude of excitatory postsynaptic potentials (EPSPs) induced by activation of NMDA or AMPA receptors, and (iv) impairs NMDA receptor-dependent LTP. Liver failure also impairs learning of the Morris water maze task. Impairment of glutamatergic synaptic transmission and NMDA receptor-mediated responses may be involved in the alterations of cognitive function in patients with liver disease.
肝病患者的认知功能会受到损害，但其机制尚不清楚。海马体中的长时程增强（LTP）被认为是某些形式学习和记忆的基础。这项研究的目的是评估：（i）慢性肝衰竭是否会损害海马体LTP；（ii）这种损害是否可能是由于谷氨酸能神经传递的改变；以及（iii）LTP的损害是否与学习能力下降有关。结果表明，Wistar大鼠的肝衰竭会在海马体中引起以下改变：（i）改变NMDA和AMPA受体的磷酸化；（ii）降低膜上NMDA和AMPA受体的表达；（iii）降低由NMDA或AMPA受体激活所诱导的兴奋性突触后电位（EPSP）的幅度；以及（iv）损害NMDA受体依赖性LTP。肝衰竭还会损害Morris水迷宫任务的学习。谷氨酸能突触传递和NMDA受体介导的反应受损可能与肝病患者认知功能的改变有关。
