Hyperammonemia impairs NMDA receptor-dependent long-term potentiation in the CA1 of rat hippocampus in vitro.
Hyperammonemia is considered the main factor responsible for the neurological and cognitive alterations found in hepatic encephalopathy and in patients with congenital deficiencies of the urea cycle enzymes. The underlying mechanisms remain unclear. Chronic moderate hyperammonemia reduces nitric oxide-induced activation of soluble guanylate cyclase and glutamate-induced formation of cGMP. NMDA receptor-associated transduction pathways, including activation of soluble guanylate cyclase, are involved in the induction of long-term potentiation (LTP), a phenomenon that is considered to be the molecular basis for some forms of memory and learning. Using an animal model we show that chronic hyperammonemia significantly reduces the degree of long-term potentiation induced in the CA1 of hippocampus slices (200% increase in control and 50% increase in slices of hyperammonemic animals). Also, addition of 1 mM ammonia impaired the maintenance of non-decremental LTP. The LTP impairment could be involved in the intellectual impairment present in chronic hepatocerebral disorders associated with hyperammonemia.
Muñoz
M D
MD
Neurología Experimental (Unidad Asociada al CSIC), Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain. dolores.munoz@hrc.es
Monfort
P
P
Gaztelu
J M
JM
Felipo
V
V
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000641:Ammonia / Q000097:blood; D000818:Animals; D002908:Chronic Disease; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015518:Rett Syndrome / Q000139:chemically induced / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D000641:Ammonia; D015763:2-Amino-5-phosphonovalerate