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Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons

Assembly of synapses requires proper coordination between pre- and postsynaptic elements. Identification of cellular and molecular events in synapse formation and maintenance is a key step to understand human perception, learning, memory, and cognition. A key role for astrocytes in synapse formation...

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Autores principales: Diniz, Luan Pereira, Almeida, Juliana Carvalho, Tortelli, Vanessa, Vargas Lopes, Charles, Setti-Perdigão, Pedro, Stipursky, Joice, Kahn, Suzana Assad, Romão, Luciana Ferreira, de Miranda, Joari, Alves-Leon, Soniza Vieira, de Souza, Jorge Marcondes, Castro, Newton G., Panizzutti, Rogério, Gomes, Flávia Carvalho Alcantara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510841/
https://www.ncbi.nlm.nih.gov/pubmed/23055518
http://dx.doi.org/10.1074/jbc.M112.380824
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author Diniz, Luan Pereira
Almeida, Juliana Carvalho
Tortelli, Vanessa
Vargas Lopes, Charles
Setti-Perdigão, Pedro
Stipursky, Joice
Kahn, Suzana Assad
Romão, Luciana Ferreira
de Miranda, Joari
Alves-Leon, Soniza Vieira
de Souza, Jorge Marcondes
Castro, Newton G.
Panizzutti, Rogério
Gomes, Flávia Carvalho Alcantara
author_facet Diniz, Luan Pereira
Almeida, Juliana Carvalho
Tortelli, Vanessa
Vargas Lopes, Charles
Setti-Perdigão, Pedro
Stipursky, Joice
Kahn, Suzana Assad
Romão, Luciana Ferreira
de Miranda, Joari
Alves-Leon, Soniza Vieira
de Souza, Jorge Marcondes
Castro, Newton G.
Panizzutti, Rogério
Gomes, Flávia Carvalho Alcantara
author_sort Diniz, Luan Pereira
collection PubMed
description Assembly of synapses requires proper coordination between pre- and postsynaptic elements. Identification of cellular and molecular events in synapse formation and maintenance is a key step to understand human perception, learning, memory, and cognition. A key role for astrocytes in synapse formation and function has been proposed. Here, we show that transforming growth factor β (TGF-β) signaling is a novel synaptogenic pathway for cortical neurons induced by murine and human astrocytes. By combining gain and loss of function approaches, we show that TGF-β1 induces the formation of functional synapses in mice. Further, TGF-β1-induced synaptogenesis involves neuronal activity and secretion of the co-agonist of the NMDA receptor, d-serine. Manipulation of d-serine signaling, by either genetic or pharmacological inhibition, prevented the TGF-β1 synaptogenic effect. Our data show a novel molecular mechanism that might impact synaptic function and emphasize the evolutionary aspect of the synaptogenic property of astrocytes, thus shedding light on new potential therapeutic targets for synaptic deficit diseases.
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spelling pubmed-35108412012-11-30 Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons Diniz, Luan Pereira Almeida, Juliana Carvalho Tortelli, Vanessa Vargas Lopes, Charles Setti-Perdigão, Pedro Stipursky, Joice Kahn, Suzana Assad Romão, Luciana Ferreira de Miranda, Joari Alves-Leon, Soniza Vieira de Souza, Jorge Marcondes Castro, Newton G. Panizzutti, Rogério Gomes, Flávia Carvalho Alcantara J Biol Chem Neurobiology Assembly of synapses requires proper coordination between pre- and postsynaptic elements. Identification of cellular and molecular events in synapse formation and maintenance is a key step to understand human perception, learning, memory, and cognition. A key role for astrocytes in synapse formation and function has been proposed. Here, we show that transforming growth factor β (TGF-β) signaling is a novel synaptogenic pathway for cortical neurons induced by murine and human astrocytes. By combining gain and loss of function approaches, we show that TGF-β1 induces the formation of functional synapses in mice. Further, TGF-β1-induced synaptogenesis involves neuronal activity and secretion of the co-agonist of the NMDA receptor, d-serine. Manipulation of d-serine signaling, by either genetic or pharmacological inhibition, prevented the TGF-β1 synaptogenic effect. Our data show a novel molecular mechanism that might impact synaptic function and emphasize the evolutionary aspect of the synaptogenic property of astrocytes, thus shedding light on new potential therapeutic targets for synaptic deficit diseases. American Society for Biochemistry and Molecular Biology 2012-11-30 2012-10-10 /pmc/articles/PMC3510841/ /pubmed/23055518 http://dx.doi.org/10.1074/jbc.M112.380824 Text en © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Neurobiology
Diniz, Luan Pereira
Almeida, Juliana Carvalho
Tortelli, Vanessa
Vargas Lopes, Charles
Setti-Perdigão, Pedro
Stipursky, Joice
Kahn, Suzana Assad
Romão, Luciana Ferreira
de Miranda, Joari
Alves-Leon, Soniza Vieira
de Souza, Jorge Marcondes
Castro, Newton G.
Panizzutti, Rogério
Gomes, Flávia Carvalho Alcantara
Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons
title Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons
title_full Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons
title_fullStr Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons
title_full_unstemmed Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons
title_short Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons
title_sort astrocyte-induced synaptogenesis is mediated by transforming growth factor β signaling through modulation of d-serine levels in cerebral cortex neurons
topic Neurobiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510841/
https://www.ncbi.nlm.nih.gov/pubmed/23055518
http://dx.doi.org/10.1074/jbc.M112.380824
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