CREB decreases astrocytic excitability by modifying subcellular calcium fluxes via the sigma-1 receptor

A. Eraso-Pichot, R. Larramona-Arcas, E. Vicario-Orri, R. Villalonga, L. Pardo, E. Galea, R. Masgrau

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

© 2016, Springer International Publishing. Astrocytic excitability relies on cytosolic calcium increases as a key mechanism, whereby astrocytes contribute to synaptic transmission and hence learning and memory. While it is a cornerstone of neurosciences that experiences are remembered, because transmitters activate gene expression in neurons, long-term adaptive astrocyte plasticity has not been described. Here, we investigated whether the transcription factor CREB mediates adaptive plasticity-like phenomena in astrocytes. We found that activation of CREB-dependent transcription reduced the calcium responses induced by ATP, noradrenaline, or endothelin-1. As to the mechanism, expression of VP16-CREB, a constitutively active CREB mutant, had no effect on basal cytosolic calcium levels, extracellular calcium entry, or calcium mobilization from lysosomal-related acidic stores. Rather, VP16-CREB upregulated sigma-1 receptor expression thereby increasing the release of calcium from the endoplasmic reticulum and its uptake by mitochondria. Sigma-1 receptor was also upregulated in vivo upon VP16-CREB expression in astrocytes. We conclude that CREB decreases astrocyte responsiveness by increasing calcium signalling at the endoplasmic reticulum–mitochondria interface, which might be an astrocyte-based form of long-term depression.
Original languageEnglish
Pages (from-to)937-950
JournalCellular and Molecular Life Sciences
Volume74
Issue number5
DOIs
Publication statusPublished - 1 Mar 2017

Keywords

  • CEPIA indicators
  • Calcium signalling
  • Endoplasmic reticulum
  • MCU
  • Mitochondria
  • Mitochondria-associated membranes
  • VP16-CREB

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