The DOI matches its Crossref record; 46 of the 47 references it cites were found in a registry or an index.
MAP Kinase Activation by Fluoxetine and Its Relation to Gene Expression in Cultured Rat Astrocytes
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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“It is known that MAPK1 activation is altered after stress [31] and corticosterone exposure [32] and that MAPK signaling was proposed to regulate AD modulation of glial cell line-derived neurotrophic factor [33].”
From The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes (2023) · cites this paper as [33]
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Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism
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Schmidt, H. D., & Duman, R. S. (2007) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3282ee2aa8 · Cited by 662
Chen, P.-S., Peng, G.-S., Li, G., Yang, S., Wu, X., Wang, C. C., Wilson, B. C., Lu, R.-B., Gean, P.-W., Chuang, D.-M., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001893 · Cited by 356
Anisman, H., Merali, Z., & Hayley, S. P. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.01.004 · Cited by 341
Hayley, S., Poulter, M. O., Merali, Z., & Anisman, H. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.03.051 · Cited by 324
Rantamäki, T., Hendolin, P., Kankaanpää, A., Mijatovic, J., Piepponen, P., Domenici, E., Chao, M. V., Männistö, P. T., & Castrén, E. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301345 · Cited by 305
Metadata
- 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 (medical) › 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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