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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Chronic hyperammonemia induces tonic activation of NMDA receptors in cerebellum
Journal of Neurochemistry, Volume 112, No. 4, Year 2010
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Description
Reduced function of the glutamate-nitric oxide (NO)-cGMP pathway is responsible for some cognitive alterations in rats with hyperammonemia and hepatic encephalopathy. Hyperammonemia impairs the pathway in cerebellum by increasing neuronal nitric oxide synthase (nNOS) phosphorylation in Ser847 by calcium-calmodulin-dependent protein kinase II (CaMKII), reducing nNOS activity, and by reducing nNOS amount in synaptic membranes, which reduces its activation following NMDA receptors activation. The reason for increased CaMKII activity in hyperammonemia remains unknown. We hypothesized that it would be as a result of increased tonic activation of NMDA receptors. The aims of this work were to assess: (i) whether tonic NMDA activation receptors is increased in cerebellum in chronic hyperammonemia in vivo; and (ii) whether this tonic activation is responsible for increased CaMKII activity and reduced activity of nNOS and of the glutamate-NO-cGMP pathway. Blocking NMDA receptors with MK-801 increases cGMP and NO metabolites in cerebellum in vivo and in slices from hyperammonemic rats. This is because of reduced phosphorylation and activity of CaMKII, leading to normalization of nNOS phosphorylation and activity. MK-801 also increases nNOS in synaptic membranes and reduces it in cytosol. This indicates that hyperammonemia increases tonic activation of NMDA receptors leading to reduced activity of nNOS and of the glutamate-NO-cGMP pathway. © 2009 International Society for Neurochemistry.
Authors & Co-Authors
ElMlili, Nisrin
Spain, Valencia
Centro de Investigacion Principe Felipe
Boix, Jordi
Spain, Valencia
Centro de Investigacion Principe Felipe
Ahabrach, Hanan
Morocco, Tetouan
Faculté Des Sciences de Tétouan
Rodrigo, Regina
Spain, Valencia
Centro de Investigacion Principe Felipe
Errami, Mohammed
Morocco, Tetouan
Faculté Des Sciences de Tétouan
Felipo, Vicente
Spain, Valencia
Centro de Investigacion Principe Felipe
Statistics
Citations: 31
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1111/j.1471-4159.2009.06520.x
ISSN:
00223042
e-ISSN:
14714159