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

Article Article scientifique Article Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission eng 2012 author Frigerio Francesca Alda 565859 author Karaca Emre Melis 718062 author De Roo Mathias 629721 author Mlynárik Vladimír author Skytt Dorte M author Carobbio Stefania 89894 author Pajęcka Kamilla author Waagepetersen Helle S author Gruetter Rolf 636584 author Muller Dominique 26488 author Maechler Pierre 0000-0002-2005-1433 76515 342-348 10.1111/j.1471-4159.2012.07933.x 22924626 0022-3042 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. Dewey 612 Dewey 616.0757 Dewey 616.8 53 Département de neurosciences fondamentales 21A 134 Département de physiologie cellulaire et métabolisme 21C 62 Département de radiologie et informatique médicale 227 false 402 Mitochondries et métabolisme énergétique 671 53 Plasticité des synapses excitatrices 76 Journal of neurochemistry 123 3 6e4b1903-0b60-424f-8575-4c61379904fd Article (Published version) Public Frigerio et al JNeurochem.pdf 496731 application/pdf openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale

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Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission	Journal of neurochemistry			2012	699	666

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Frigerio, Francesca Alda