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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)

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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

Corresponding Author

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

ISSN (print) / ISBN 0306-4522

e-ISSN 1873-7544

Journal Neuroscience

Quellenangaben Volume: 447, Pages: 182-190

Publisher International Brain Research Organization, Elsevier

Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)