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

作者：Diniz Luan Pereira; Almeida Juliana Carvalho; Tortelli Vanessa; Lopes Charles Vargas; Setti Perdigao Pedro; Stipursky Joice; Kahn Suzana Assad; Romao Luciana Ferreira; de Miranda Joari; Alves Leon Soniza Vieira; de Souza Jorge Marcondes; Castro Newton G; Panizzutti Rogerio; Alcantara Gomes Flavia Carvalho

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287(49): 41432-41445.

DOI：10.1074/jbc.M112.380824

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 beta (TGF-beta) 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-beta 1 induces the formation of functional synapses in mice. Further, TGF-beta 1-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-beta 1 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.

• 出版日期2012-11-30