Ammonium-induced impairment of axonal growth is prevented through glial creatine.

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Version: Author's accepted manuscript
Secondary document(s)
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Version: Final published version
Serval ID
serval:BIB_5EC36D0C3C26
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ammonium-induced impairment of axonal growth is prevented through glial creatine.
Journal
The Journal of neuroscience
Author(s)
Braissant O., Henry H., Villard A.M., Zurich M.G., Loup M., Eilers B., Parlascino G., Matter E., Boulat O., Honegger P., Bachmann C.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Publication state
Published
Issued date
15/11/2002
Peer-reviewed
Oui
Volume
22
Number
22
Pages
9810-9820
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Hyperammonemia in neonates and infants affects brain development and causes mental retardation. We report that ammonium impaired cholinergic axonal growth and altered localization and phosphorylation of intermediate neurofilament protein in rat reaggregated brain cell primary cultures. This effect was restricted to the phase of early maturation but did not occur after synaptogenesis. Exposure to NH4Cl decreased intracellular creatine, phosphocreatine, and ADP. We demonstrate that creatine cotreatment protected axons from ammonium toxic effects, although this did not restore high-energy phosphates. The protection by creatine was glial cell-dependent. Our findings suggest that the means to efficiently sustain CNS creatine concentration in hyperammonemic neonates and infants should be assessed to prevent impairment of axonogenesis and irreversible brain damage.

Keywords
Adenosine Diphosphate/metabolism, Adenosine Monophosphate/metabolism, Adenosine Triphosphate/metabolism, Ammonium Chloride/toxicity, Animals, Axons/drug effects, Axons/metabolism, Axons/physiology, Cell Differentiation/physiology, Cell Division/drug effects, Cells, Cultured, Choline O-Acetyltransferase/biosynthesis, Coculture Techniques, Creatine/metabolism, Creatine/pharmacology, Dose-Response Relationship, Drug, GAP-43 Protein/biosynthesis, Glucose/pharmacokinetics, Immunohistochemistry, Intracellular Fluid/metabolism, Lactic Acid/metabolism, Neurofilament Proteins/biosynthesis, Neuroglia/cytology, Neuroglia/metabolism, Neurons/cytology, Neurons/drug effects, Neurons/metabolism, Phosphocreatine/metabolism, Quaternary Ammonium Compounds/pharmacokinetics, Rats, Telencephalon/cytology, Telencephalon/embryology
Pubmed
Web of science
Create date
25/04/2008 10:40
Last modification date
20/08/2019 14:16
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