zaprinast and 3-4-dihydroxyphenylglycol

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.

Topics: Ammonia; Animals; Antioxidants; Biophysics; Cerebral Cortex; Corpus Striatum; Cycloheximide; Drug Interactions; Electric Stimulation; In Vitro Techniques; Long-Term Synaptic Depression; Male; Methoxyhydroxyphenylglycol; Mice; Mice, Inbred C57BL; Phosphodiesterase Inhibitors; Polyphenols; Protein Synthesis Inhibitors; Purinones; Synapses