Brain-derived neurotrophic factor protection of cortical neurons from serum withdrawal-induced apoptosis is inhibited by cAMP

Steven Poser, Soren Impey, Zhengui Xia, Daniel R. Storm

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Programmed cell death plays an important role both during the development of the CNS and in its homeostasis throughout adulthood. A complex balance between cell death- and survival-inducing signals determines the fate of individual neurons. Intracellular cAMP is thought to regulate neuronal survival, and previous studies have shown that the survival of retinal ganglion cells by brain-derived neurotrophic factor (BDNF) is dependent on cAMP. Here we report the surprising observation that cAMP attenuates the ability of BDNF to rescue cortical neurons from apoptosis after serum deprivation, a process mediated via the phosphatidylinositol 3 (PI3)-kinase signal transduction cascade. Depolarization by KCl, which increases cAMP in cortical neurons, also attenuates BDNF protection against serum withdrawal. Our data indicate that cAMP antagonizes neurotrophin protection from serum withdrawal by inhibiting the PI3-kinase signal transduction cascade. This study indicates that cAMP may inhibit some forms of neurotrophin-mediated neuronal survival and suggests that a number of PI3-kinase-regulated processes in neurons may be inhibited by cAMP.

Original languageEnglish (US)
Pages (from-to)4420-4427
Number of pages8
JournalJournal of Neuroscience
Volume23
Issue number11
StatePublished - Jun 1 2003

Keywords

  • Apoptosis
  • Coincident signaling
  • Neurotrophins
  • PI3-kinase
  • Survival
  • cAMP

ASJC Scopus subject areas

  • Neuroscience(all)

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