Journal of Molecular Neuroscience

, Volume 24, Issue 2, pp 207–216

MAP kinase activation by fluoxetine and its relation to gene expression in cultured rat astrocytes

  • Gilles Mercier
  • Anna Maria Lennon
  • Benjamin Renouf
  • Audrey Dessouroux
  • Martine Ramaugé
  • Françoise Courtin
  • Michel Pierre
Original Article

DOI: 10.1385/JMN:24:2:207

Cite this article as:
Mercier, G., Lennon, A.M., Renouf, B. et al. J Mol Neurosci (2004) 24: 207. doi:10.1385/JMN:24:2:207

Abstract

Chronic treatments with antidepressants active on major depressive disorders influence pathways involved in cell survival and plasticity. As astrocytes seem to play a key role in the protection of brain cells, we investigated in these cells the rapid effects of the antidepressant fluoxetine (Prozac®) on signaling cascades and gene induction, which probably play a role in neuroprotection. We show here that fluoxetine alone activates the extracellular signal-regulated-protein kinase (Erk) and p38 mitogen-associated protein (MAP) kinase cascades. RT-PCR revealed that genes, modulated in brain by long-term fluoxetine treatment, are rapidly induced (detectable after 2–4 h) by fluoxetine in cultured astrocytes: brain-derived nerve factor (BDNF) and its receptors, glialderived nerve factor (GDNF) and deiodinase 3 (D3). Induction of D3 by fluoxetine is inhibited by U0126 and SB203580, suggesting that Erk and p38 MAP kinases are involved. Glial-derived nerve factor (GDNF) induction by fluoxetine is prevented by U0126, suggesting that Erk is implicated. Brain-derived nerve factor (BDNF) induction seems mediated by other signaling pathways. In conclusion, we show that fluoxetine alone rapidly activates mitogen activated protein (MAP) kinase cascades in rat astrocytes and that genes involved in neuroprotection are induced in a few hours in a MAP kinase-dependent or -independent manner.

Index Entries

Antidepressants astrocytes MAP kinase BDNF GDNF D3 

Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Gilles Mercier
    • 1
  • Anna Maria Lennon
    • 1
  • Benjamin Renouf
    • 1
  • Audrey Dessouroux
    • 1
  • Martine Ramaugé
    • 1
  • Françoise Courtin
    • 1
  • Michel Pierre
    • 1
  1. 1.Unité de Recherche Stéroïdes et Système Nerveux, Unité 488 de l’Institut National de la Santé et de la Recherche Médicale (INSERM)Le Kremlin-BicêtreFrance