Molecular mechanisms of the alterations in NMDA receptor-dependent long-term potentiation in hyperammonemia

Long-term potentiation (LTP) is a long-lasting enhancement of synaptic transmission efficacy and is considered the base for some forms of learning and memory. Hyperammonemia impairs LTP in hippocampus. Proper LTP induction in hippocampal slices requires activation of the soluble guanylate cyclase (s...

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Bibliographic Details
Published in:Metabolic brain disease 2005-12, Vol.20 (4), p.265-274
Main Authors: MONFORT, Pilar, MUNOZ, Maria-Dolores, FELIPO, Vicente
Format: Article
Language:English
Subjects:
3',5'-Cyclic-GMP Phosphodiesterases - metabolism
Animals
Biological and medical sciences
Blood. Blood coagulation. Reticuloendothelial system
Cyclic GMP-Dependent Protein Kinases - metabolism
Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology
Guanylate Cyclase - metabolism
Hippocampus - physiology
Humans
Hyperammonemia - metabolism
Hyperammonemia - psychology
In Vitro Techniques
Long-Term Potentiation - drug effects
Long-Term Potentiation - physiology
Medical sciences
Neurology
Non tumoral diseases
Otorhinolaryngology. Stomatology
Pharmacology. Drug treatments
Receptors, N-Methyl-D-Aspartate - drug effects
Receptors, N-Methyl-D-Aspartate - physiology
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Summary:Long-term potentiation (LTP) is a long-lasting enhancement of synaptic transmission efficacy and is considered the base for some forms of learning and memory. Hyperammonemia impairs LTP in hippocampus. Proper LTP induction in hippocampal slices requires activation of the soluble guanylate cyclase (sGC)-protein kinase G (PKG)-cyclic guanosine monophosphate (cGMP)-degrading phosphodiesterase pathway. Hyperammonemia impairs LTP by impairing the tetanus-induced activation of this pathway. The tetanus induces a rapid cGMP rise, reaching a maximum at 10 s, both in the absence or in the presence of ammonia. The increase in cGMP is followed, in control slices, by a sustained decrease in cGMP because of PKG-mediated activation of cGMP-degrading phosphodiesterase, which is required for maintenance of LTP. Hyperammonemia prevents completely tetanus-induced decrease in cGMP by impairing PKG-mediated activation of cGMP-degrading phosphodiesterase. Addition of 8 Br-cGMP to slices treated with ammonia restores both phosphodiesterase activation and maintenance of LTP. Impairment of LTP in hyperammonemia may be involved in the impairment of the cognitive function in patients with hepatic encephalopathy.
ISSN:0885-7490
1573-7365
DOI:10.1007/s11011-005-7905-5