Specific Deletion of the Astrocyte Leptin Receptor Induces Changes in Hippocampus Glutamate Metabolism, Synaptic Transmission and Plasticity

•Astrocyte LepR deletion reduces basal synaptic transmission in the hippocampus.•Astrocyte LepR modulate NMDA-induced LTD within the hippocampus.•Astrocyte LepR regulate the expression of the glutamate transporter GLT-1.•Astrocyte LepR are involved in glutamate uptake and neurotransmission. The aim...

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Published in:Neuroscience 2020-11, Vol.447, p.182-190
Main Authors: Naranjo, Víctor, Contreras, Ana, Merino, Beatriz, Plaza, Adrián, Lorenzo, María P., García-Cáceres, Cristina, García, Antonia, Chowen, Julie A., Ruiz-Gayo, Mariano, Del Olmo, Nuria, Cano, Victoria
Format: Article
Language:English
Subjects:
Animals
astrocyte
Astrocytes - metabolism
glutamate metabolism
glutamate transmission
hippocampus
Hippocampus - metabolism
leptin
Mice
Neuronal Plasticity
Receptors, Leptin - genetics
Receptors, N-Methyl-D-Aspartate - metabolism
Synaptic Transmission
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Summary:•Astrocyte LepR deletion reduces basal synaptic transmission in the hippocampus.•Astrocyte LepR modulate NMDA-induced LTD within the hippocampus.•Astrocyte LepR regulate the expression of the glutamate transporter GLT-1.•Astrocyte LepR are involved in glutamate uptake and neurotransmission. 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.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2019.10.005