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

Mlynárik, Vladimír
Skytt, Dorte M
Pajęcka, Kamilla
Waagepetersen, Helle S
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Published in Journal of Neurochemistry. 2012, vol. 123, no. 3, p. 342-8
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.
PMID: 22924626
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Article (Published version) (485 Kb) - public document Free access
Research groups Mitochondries et sécrétion d'insuline (671)
Plasticité des synapses excitatrices (76)
(ISO format)
FRIGERIO, Francesca Alda et al. Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission. In: Journal of Neurochemistry, 2012, vol. 123, n° 3, p. 342-8. doi: 10.1111/j.1471-4159.2012.07933.x https://archive-ouverte.unige.ch/unige:26263

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Deposited on : 2013-02-06

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