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Naranjo, V.* ; Contreras, A.* ; Merino, B.* ; Plaza, A.* ; Lorenzo, M.P.* ; García-Cáceres, C. ; García, A.* ; Chowen, J.A.* ; Ruiz-Gayo, M.* ; Del Olmo, N.* ; Cano, V.*

Specific deletion of the astrocyte leptin receptor induces changes in hippocampus glutamate metabolism, synaptic transmission and plasticity.

Neuroscience 447, 182-190 (2020)
Postprint DOI
Open Access Green
The aim of this study was to indentify the involvement of leptin receptors (LepR) in astrocytes in hippocampal synaptic transmission and plasticity and metabolism. To this end we used a genetic mouse model (GFAP-LepR(-/-)) of specific LepR ablation in GFAP positive cells and recorded excitatory postsynaptic potentials (fEPSPs) within the CA1 area. Glutamate (Glu) uptake and the expression of Glu transporters (EEAT3, GLT-1 and GLAST) and enzymes involved in Glu metabolism (glutamine synthase, GABA decarboxylase 65 and 67) were quantified. Modifications in the expression of GFAP, the glucose transporter (GLUT)-1, and the monocarboxylate transporters MCT-2 and MCT-4, were also analyzed. The results show that depletion of LepR in GFAP positive cells reduced basal synaptic transmission within the CA1 area and impaired N-methyl-D-aspartate (NMDA)-evoked long-term depression (NMDA-LTD). Hippocampal slices from GFAP-LepR(-/-) mice displayed lower Glu uptake efficacy together with up-regulation of GLT-1, glutamine synthase, GFAP and GLUT-1. In conclusion, astrocyte LepRs are involved in the maintenance of Glu homeostasis and Glu neurotransmission within the hippocampus. Our findings support a role of hippocampal LepRs in synaptic plasticity, which could have an impact on memory and learning processes.This article is part of a Special Issue entitled: The Neuroscience of Energy Balance and Eating Behavior (C) 2019 IBRO.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Leptin ; Hippocampus ; Astrocyte ; Glutamate Metabolism ; Glutamate Transmission; Long-term Potentiation; High-fat Diets; Messenger-rna; Spatial Memory; Up-regulation; Glucose; Expression; Lactate; Localization; Transport
ISSN (print) / ISBN 0306-4522
e-ISSN 1873-7544
Zeitschrift Neuroscience
Quellenangaben Band: 447, Heft: , Seiten: 182-190 Artikelnummer: , Supplement: ,
Verlag International Brain Research Organization, Elsevier
Verlagsort The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)