Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission.

Details

Serval ID
serval:BIB_B8A977F5C183
Type
Article: article from journal or magazin.
Collection
Publications
Title
Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission.
Journal
Journal of Neurochemistry
Author(s)
Frigerio F., Karaca M., De Roo M., Mlynárik V., Skytt D.M., Carobbio S., Pajęcka K., Waagepetersen H.S., Gruetter R., Muller D., Maechler P.
ISSN
1471-4159 (Electronic)
ISSN-L
0022-3042
Publication state
Published
Issued date
2012
Volume
123
Number
3
Pages
342-348
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish. PDF type: Short Communication
Abstract
Glutamate dehydrogenase (GDH), encoded by GLUD1, participates in the breakdown and synthesis of glutamate, the main excitatory neurotransmitter. In the CNS, besides its primary signaling function, glutamate is also at the crossroad of metabolic and neurotransmitter pathways. Importance of brain GDH was questioned here by generation of CNS-specific GDH-null mice (CnsGlud1(-/-)); which were viable, fertile and without apparent behavioral problems. GDH immunoreactivity as well as enzymatic activity were absent in Cns-Glud1(-/-) brains. Immunohistochemical analyses on brain sections revealed that the pyramidal cells of control animals were positive for GDH, whereas the labeling was absent in hippocampal sections of Cns-Glud1(-/-) mice. Electrophysiological recordings showed that deletion of GDH within the CNS did not alter synaptic transmission in standard conditions. Cns-Glud1(-/-) mice exhibited deficient oxidative catabolism of glutamate in astrocytes, showing that GDH is required for Krebs cycle pathway. As revealed by NMR studies, brain glutamate levels remained unchanged, whereas glutamine levels were increased. This pattern was favored by up-regulation of astrocyte-type glutamate and glutamine transporters and of glutamine synthetase. Present data show that the lack of GDH in the CNS modifies the metabolic handling of glutamate without altering synaptic transmission.
Keywords
Animals, Brain/enzymology, Brain/pathology, Cells, Cultured, Female, Gene Deletion, Glutamic Acid/metabolism, Glutamine/metabolism, Male, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Neural Pathways/metabolism, Neural Pathways/pathology, Organ Culture Techniques, Receptors, Glutamate/deficiency, Receptors, Glutamate/genetics, Synaptic Transmission/genetics, Synaptic Transmission/physiology
Pubmed
Web of science
Create date
29/04/2013 9:41
Last modification date
20/08/2019 15:26
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