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 oxi...

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Bibliographic Details
Published in:Neurochemical research 2000-04, Vol.25 (4), p.437-441
Main Authors: MUNOZ, M.-D, MONFORT, P, GAZTELU, J.-M, FELIPO, V
Format: Article
Language:English
Subjects:
2-Amino-5-phosphonovalerate - pharmacology
Ammonia - blood
Animals
Biological and medical sciences
Chronic Disease
Electric Stimulation
Errors of metabolism
Excitatory Postsynaptic Potentials - drug effects
Hepatic Encephalopathy - metabolism
Hippocampus - drug effects
Hippocampus - metabolism
hyperammonemia
In Vitro Techniques
Long-Term Potentiation - drug effects
Long-Term Potentiation - physiology
Medical sciences
Metabolic diseases
Miscellaneous hereditary metabolic disorders
Rats
Rats, Wistar
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - metabolism
Rett Syndrome - chemically induced
Rett Syndrome - metabolism
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Summary: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.
ISSN:0364-3190
1573-6903
DOI:10.1023/A:1007547622844