• Víctor Naranjo, Ana Contreras, Beatriz Merino, Adrián Plaza, María P Lorenzo, Cristina García-Cáceres, Antonia García, Julie A Chowen, Mariano Ruiz-Gayo, Nuria Del Olmo, and Victoria Cano.
• Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.
• Neuroscience. 2020 Nov 1; 447: 182-190.

AbstractThe 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.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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