Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy
Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy
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DOI：
10.1007/s11011-008-9115-4
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发表时间：
2009-03-01
影响因子：
3.6
通讯作者：
Felipo, Vicente
中科院分区：
文献类型：
--
作者：
Cauli, Omar;Rodrigo, Regina;Felipo, Vicente
肝性脑病（HE）患者可能会出现不同的神经系统改变，包括认知功能受损和运动活动和协调性改变。他可能会导致昏迷和死亡。许多神经系统的改变是神经传递改变的结果。高氨血症是HE中神经传递和神经功能改变的主要原因。在HE动物模型中，谷氨酸能和GABA能神经传递均发生改变。我们综述了其中的一些改变，特别是在高氨血症和HE中引起某些特定神经学改变的谷氨酸能神经传递的改变：1）NMDA受体过度激活在急性高氨血症诱导的死亡中的作用; 2）与NMDA受体相关的谷氨酸-一氧化氮-cGMP通路功能受损在慢性HE认知障碍中的作用;（3）慢性HE运动功能减退时细胞外谷氨酸增加和黑质代谢型谷氨酸受体激活。的治疗意义进行了讨论。我们还审查了基底神经节-丘脑-皮层之间的神经元回路的功能的改变，调节运动活动和顺序改变在这些改变中的作用amatergic和GABA能神经传递。HE可能是由于涉及不同神经元中不同神经递质系统的一般神经传递改变而导致神经元通信改变的结果。
Patients with hepatic encephalopathy (HE) may present different neurological alterations including impaired cognitive function and altered motor activity and coordination. HE may lead to coma and death. Many of these neurological alterations are the consequence of altered neurotransmission. Hyperammonemia is a main contributor to the alterations in neurotransmission and in neurological functions in HE. Both glutamatergic and GABAergic neurotransmission are altered in animal models of HE. We review some of these alterations, especially those alterations in glutamatergic neurotransmission responsible for some specific neurological alterations in hyperammonemia and HE: the role 1) of excessive NMDA receptors activation in death induced by acute hyperammonemia; 2) of impaired function of the glutamate-nitric oxide-cGMP pathway, associated to NMDA receptors, in cognitive impairment in chronic HE; 3) of increased extracellular glutamate and activation of metabotropic glutamate receptors in substantia nigra in hypokinesia in chronic HE. The therapeutic implications are discussed. We also review the alterations in the function of the neuronal circuits between basal ganglia-thalamus-cortex modulating motor activity and the role of sequential alterations in glutamatergic and GABAergic neurotransmission in these alterations. HE would be a consequence of altered neuronal communication due to alterations in general neurotransmission involving different neurotransmitter systems in different neurons.