RT Journal Article
SR Electronic
T1 Ammonium-Induced Impairment of Axonal Growth Is Prevented through Glial Creatine
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9810
OP 9820
DO 10.1523/JNEUROSCI.22-22-09810.2002
VO 22
IS 22
A1 Olivier Braissant
A1 Hugues Henry
A1 Anne-Marie Villard
A1 Marie-Gabrielle Zurich
A1 Marc Loup
A1 Barbara Eilers
A1 Gianni Parlascino
A1 Edouard Matter
A1 Olivier Boulat
A1 Paul Honegger
A1 Claude Bachmann
YR 2002
UL http://www.jneurosci.org/content/22/22/9810.abstract
AB 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.