Department of Neurophysiology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany.
J Neurochem. 2012 Aug;122(3):545-56. doi: 10.1111/j.1471-4159.2012.07806.x. Epub 2012 Jun 12.
Hyperammonemia is a major pathophysiological factor in encephalopathies associated with acute and chronic liver failure. On mouse brain slice preparations, we analyzed the effects of ammonia on the characteristics of corticostriatal long-term depression (LTD) induced by electrical stimulation of cortical input or pharmacological activation of metabotropic glutamate receptors. Long exposure of neostriatal slices to ammonium chloride impaired the induction and/or expression of all studied forms of LTD. This impairment was reversed by the phosphodiesterase inhibitor zaprinast implying lowered cGMP signaling in LTD suppression. Polyphenols from green tea rescued short-term corticostriatal plasticity, but failed to prevent the ammonia-induced deficit of LTD. Zaprinast counteracts the ammonia-induced impairment of long-term corticostriatal plasticity and may thus improve fine motor skills and procedural learning in hepatic encephalopathy.
高氨血症是与急性和慢性肝功能衰竭相关脑病的主要病理生理因素。在小鼠脑片标本上，我们分析了氨对皮质输入电刺激或代谢型谷氨酸受体药理学激活诱导的皮质纹状体长时程抑制（LTD）特征的影响。新纹状体切片长时间暴露于氯化铵中会损害所有研究形式的 LTD 的诱导和/或表达。这种损伤可被磷酸二酯酶抑制剂扎普司特逆转，提示 LTD 抑制时 cGMP 信号降低。绿茶中的多酚挽救了短期皮质纹状体可塑性，但未能防止氨诱导的 LTD 缺陷。扎普司特可拮抗氨诱导的长期皮质纹状体可塑性损伤，从而可能改善肝性脑病的精细运动技能和程序性学习。
