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Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro

Glucagon-like peptide-1 (GLP-1) is mainly secreted by preproglucagon neurons; it plays important roles in modulating neuronal activity and synaptic transmission through its receptors. In the present study, we investigated the effects of GLP-1 on parallel fiber–Purkinje cell (PF-PC) synaptic transmis...

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Autores principales: Wang, Xin-Yuan, Liu, Yang, Cao, Li-Xin, Li, Yu-Zi, Wan, Peng, Qiu, De-Lai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188593/
https://www.ncbi.nlm.nih.gov/pubmed/37193712
http://dx.doi.org/10.1038/s41598-023-34070-6
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author Wang, Xin-Yuan
Liu, Yang
Cao, Li-Xin
Li, Yu-Zi
Wan, Peng
Qiu, De-Lai
author_facet Wang, Xin-Yuan
Liu, Yang
Cao, Li-Xin
Li, Yu-Zi
Wan, Peng
Qiu, De-Lai
author_sort Wang, Xin-Yuan
collection PubMed
description Glucagon-like peptide-1 (GLP-1) is mainly secreted by preproglucagon neurons; it plays important roles in modulating neuronal activity and synaptic transmission through its receptors. In the present study, we investigated the effects of GLP-1 on parallel fiber–Purkinje cell (PF-PC) synaptic transmission in mouse cerebellar slices using whole-cell patch-clamp recording and pharmacology methods. In the presence of a γ-aminobutyric acid type A receptor antagonist, bath application of GLP-1 (100 nM) enhanced PF-PC synaptic transmission, with an increased amplitude of evoked excitatory postsynaptic synaptic currents (EPSCs) and a decreased paired-pulse ratio. The GLP-1-induced enhancement of evoked EPSCs was abolished by a selective GLP-1 receptor antagonist, exendin 9–39, as well as by the extracellular application of a specific protein kinase A (PKA) inhibitor, KT5720. In contrast, inhibiting postsynaptic PKA with a protein kinase inhibitor peptide-containing internal solution failed to block the GLP-1-induced enhancement of evoked EPSCs. In the presence of a mixture of gabazine (20 μM) and tetrodotoxin (1 μM), application GLP-1 significantly increased frequency, but not amplitude of miniature EPSCs via PKA signaling pathway. The GLP-1-induced increase in miniature EPSC frequency was blocked by both exendin 9–39 and KT5720. Together, our results indicate that GLP-1 receptor activation enhances glutamate release at PF-PC synapses via the PKA signaling pathway, resulting in enhanced PF-PC synaptic transmission in mice in vitro. These findings suggest that, in living animals, GLP-1 has a critical role in the modulation of cerebellar function by regulating excitatory synaptic transmission at PF-PC synapses.
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spelling pubmed-101885932023-05-18 Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro Wang, Xin-Yuan Liu, Yang Cao, Li-Xin Li, Yu-Zi Wan, Peng Qiu, De-Lai Sci Rep Article Glucagon-like peptide-1 (GLP-1) is mainly secreted by preproglucagon neurons; it plays important roles in modulating neuronal activity and synaptic transmission through its receptors. In the present study, we investigated the effects of GLP-1 on parallel fiber–Purkinje cell (PF-PC) synaptic transmission in mouse cerebellar slices using whole-cell patch-clamp recording and pharmacology methods. In the presence of a γ-aminobutyric acid type A receptor antagonist, bath application of GLP-1 (100 nM) enhanced PF-PC synaptic transmission, with an increased amplitude of evoked excitatory postsynaptic synaptic currents (EPSCs) and a decreased paired-pulse ratio. The GLP-1-induced enhancement of evoked EPSCs was abolished by a selective GLP-1 receptor antagonist, exendin 9–39, as well as by the extracellular application of a specific protein kinase A (PKA) inhibitor, KT5720. In contrast, inhibiting postsynaptic PKA with a protein kinase inhibitor peptide-containing internal solution failed to block the GLP-1-induced enhancement of evoked EPSCs. In the presence of a mixture of gabazine (20 μM) and tetrodotoxin (1 μM), application GLP-1 significantly increased frequency, but not amplitude of miniature EPSCs via PKA signaling pathway. The GLP-1-induced increase in miniature EPSC frequency was blocked by both exendin 9–39 and KT5720. Together, our results indicate that GLP-1 receptor activation enhances glutamate release at PF-PC synapses via the PKA signaling pathway, resulting in enhanced PF-PC synaptic transmission in mice in vitro. These findings suggest that, in living animals, GLP-1 has a critical role in the modulation of cerebellar function by regulating excitatory synaptic transmission at PF-PC synapses. Nature Publishing Group UK 2023-05-16 /pmc/articles/PMC10188593/ /pubmed/37193712 http://dx.doi.org/10.1038/s41598-023-34070-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Xin-Yuan
Liu, Yang
Cao, Li-Xin
Li, Yu-Zi
Wan, Peng
Qiu, De-Lai
Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro
title Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro
title_full Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro
title_fullStr Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro
title_full_unstemmed Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro
title_short Glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through PKA signaling in mice in vitro
title_sort glucagon-like peptide-1 facilitates cerebellar parallel fiber glutamate release through pka signaling in mice in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188593/
https://www.ncbi.nlm.nih.gov/pubmed/37193712
http://dx.doi.org/10.1038/s41598-023-34070-6
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