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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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Detalles Bibliográficos
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
Descripción
Sumario: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.