Ammonia toxicity to the brain and creatine.

Détails

Ressource 1Télécharger: BIB_B883374CE062.P001.pdf (60.24 [Ko])
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_B883374CE062
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Ammonia toxicity to the brain and creatine.
Périodique
Molecular Genetics and Metabolism
Auteur⸱e⸱s
Bachmann C., Braissant O., Villard A.M., Boulat O., Henry H.
ISSN
1096-7192 (Print)
ISSN-L
1096-7192
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
81
Numéro
Suppl 1
Pages
S52-S57
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Résumé
Symptoms of hyperammonemia are age-dependent and some are reversible. Multiple mechanisms are involved. Hyperammonemia increases the uptake of tryptophan into the brain by activation of the L-system carrier while brain glutamine plays a still undefined role. The uptake of tryptophan by the brain is enhanced when the plasma levels of branched-chain amino acids competing with the other large neutral amino acids are low. Hyperammonemia increases the utilization of branched-chain amino acids in muscle when ketoglutarate is low, and this is further enhanced by glutamine depletion (as a result of therapy with ammonia scavengers like phenylbutyrate). Anorexia, most likely a serotoninergic symptom, might further aggravate the deficiency of indispensable amino acids (e.g., branched-chain and arginine). The role of increased glutamine production in astrocytes and the excitotoxic and metabotropic effects of increased extracellular glutamate have been extensively investigated and found to differ between models of acute and chronic hyperammonemia. Using an in vitro model of cultured embryonic rat brain cell aggregates, we studied the role of creatine in ammonia toxicity. Cultures exposed to ammonia before maturation showed impaired cholinergic axonal growth accompanied by a decrease of creatine and phosphocreatine, a finding not observed in mature cultures. By using different antibodies, we have shown that the phosphorylated form of the intermediate neurofilament protein is affected. Adding creatine to the culture medium partially prevents impairment of axonal growth and the presence of glia in the culture is a precondition for this protective effect. Adequate arginine substitution is essential in the treatment of urea cycle defects as creatine is inefficiently transported into the brain.
Mots-clé
Ammonia/blood, Ammonia/toxicity, Animals, Brain Chemistry, Creatine/blood, Creatine/metabolism, Culture Media, Serum-Free, Glutamic Acid/metabolism, Hyperammonemia/metabolism, Plasma/metabolism, Rats, Tryptophan/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 20:49
Dernière modification de la notice
20/08/2019 15:26
Données d'usage