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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Leptin ; Hippocampus ; Astrocyte ; Glutamate Metabolism ; Glutamate Transmission; Long-term Potentiation; High-fat Diets; Messenger-rna; Spatial Memory; Up-regulation; Glucose; Expression; Lactate; Localization; Transport
Language english
Publication Year 2020
Prepublished in Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 0306-4522
e-ISSN 1873-7544
Journal Neuroscience
Quellenangaben Volume: 447, Issue: , Pages: 182-190 Article Number: , Supplement: ,
Publisher International Brain Research Organization, Elsevier
Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502200-001
DOI 10.1016/j.neuroscience.2019.10.005
WOS ID WOS:000579946800016
Scopus ID 85075439638
Erfassungsdatum 2019-12-03
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