Cited by 176Treatment of Major DepressionNeuroscience and Neuropharmacology ResearchTryptophan and brain disorders

MAP Kinase Activation by Fluoxetine and Its Relation to Gene Expression in Cultured Rat Astrocytes

Mercier, Gilles, Lennon, Anna Maria, Renouf, Benjamin, Dessouroux, Audrey, Ramaugé, Martine, Courtin, Françoise, Pierre, Michel·2004·Journal of Molecular Neuroscience

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 by fluoxetine in cultured astrocytes: brain-derived nerve factor (BDNF) and its receptors, glial-derived 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.

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Crossref · 10.1385/jmn:24:2:207

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Authors
Mercier, G., Lennon, A. M., Renouf, B., Dessouroux, A., Ramaugé, M., Courtin, F., & Pierre, M.
Affiliations
Inserm (FR)
Corresponding author
Mercier, Gilles
Venue
Journal of Molecular Neuroscience
Published
2004
Volume
24
Issue
2
Pages
207-216
ISSN
0895-8696 (ISSN-L)
OpenAlex
W1996567906
Cited by
176
References
47
Citations by year
2026: 4 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 6 · 2018: 6 · 2017: 8 · 2016: 6 · 2015: 10 · 2014: 19 · 2013: 11 · 2012: 14
FWCI
7.28
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Molecular Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
fluoxetine, astrocytes, MAPK signaling, ERK, p38 MAPK, antidepressants, neuroprotection, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, gene expression, major depressive disorder, U0126, SB203580
MeSH terms
Animals, Astrocytes, Cells, Cultured, Enzyme Activation, Fluoxetine, Gene Expression Regulation, Nerve Growth Factors, Nerve Tissue Proteins, Proto-Oncogene Proteins, Signal Transduction, Transcriptional Activation, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Antidepressive Agents, Second-Generation, Brain-Derived Neurotrophic Factor, Receptor, trkB, Mitogen-Activated Protein Kinases, Extracellular Signal-Regulated MAP Kinases, p38 Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Glial Cell Line-Derived Neurotrophic Factor, Rats

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