Ammonia-induced deficit in corticostriatal long-term depression and its amelioration by zaprinast.
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.
Department of Neurophysiology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany.
Aisa N
AN
Chepkova
Oliver
O
Selbach
Helmut L
HL
Haas
Olga A
OA
Sergeeva
D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001703:Biophysics; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects*
D000975:Antioxidants; D010726:Phosphodiesterase Inhibitors; D059808:Polyphenols; D011500:Protein Synthesis Inhibitors; D011688:Purinones; D008734:Methoxyhydroxyphenylglycol; D000641:Ammonia; D003513:Cycloheximide; C011145:zaprinast; C010117:3,4-dihydroxyphenylglycol