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Cited by 72Nerve injury and regenerationTreatment of Major DepressionNeurogenesis and neuroplasticity mechanisms

Serotonin and neuronal growth factors—a convergence of signaling pathways

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Cowen, Daniel S.·2007·Journal of Neurochemistry
DOI 10.1111/j.1471-4159.2006.04420.x
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Abstract

Monoamines, including serotonin (5‐HT), have traditionally been associated with short‐term signaling pathways in neurons, such as the modulation of cAMP and Ca 2+levels. In contrast, neuronal growth factors, such as neurotrophins, have been traditionally associated with signaling pathways, such as those for activation of extracellular‐regulated kinase (ERK) and Akt (protein kinase B), which are known to induce long‐term protective changes. It has therefore been unclear how antidepressants that increase serotonin (5‐HT), induce such changes as hippocampal neuroprotection and neurogenesis. It has been hypothesized, that the actions of 5‐HT may be mediated indirectly through increased synthesis of peptide growth factors. However, there is increasing evidence that some subtypes of 5‐HT receptors can directly couple to activation of the ERK and Akt pathways. Such coupling suggests a more direct potential role for 5‐HT in mediating the long‐term actions induced by antidepressants.

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Crossref · 10.1111/j.1471-4159.2006.04420.x

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  • TrkB activation induces downstream pathways including the PI3K/Akt pathway, which is linked to the Wnt/β-catenin and mTOR pathways.

    “The TrkB activation induces downstream pathways, including the PI3K/Akt pathway, which is linked to the Wnt/β-catenin and to the mTOR pathway [4,16].”

    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 [16]

    The Abstract (page unavailable) reports that BDNF activates Akt and that Akt activation requires PI3K, supporting the growth-factor-to-PI3K/Akt part of the claim. Our copy does not identify TrkB as the receptor in that passage or establish a link from this pathway to Wnt/β-catenin or mTOR; mTOR appears only in a reference about serotonin-induced growth in smooth muscle. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Some serotonergic receptors modulate the activity of signaling pathways involved in neuronal plasticity such as ERK or MAPK.

    “Some serotonergic receptors, beyond their traditional association with G proteins, modulate the activity of signaling pathways involved in neuronal plasticity such as extracellular-regulated kinase (ERK) or mitogen-activated protein kinase (MAPK, Cowen, 2007;Polter and Li, 2010).”

    From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Cowen, 2007

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Research works printed but not linked: 4

  1. [9]9. Berends A. C., Luiten P. G. and Nyakas C. (2005) A review of the neuroprotective properties of the 5-HT1A receptor agonist re- pinotan HCl (BAYx3702) in ischemic stroke. CNS Drug Rev. 11, 379-402.
  2. [11]11. Brunet A., Bonni A., Zigmond M. J., Lin M. Z., Juo P., Hu L. S., Anderson M. J., Arden K. C., Blenis J. and Greenberg M. E. 1168 D. S. Cowen Journal Compilation Ó 2007 International Society for Neurochemistry, J. Neurochem. (2007) 101, 1161-1171
  3. [78]78. D. S. Cowen Journal Compilation Ó 2007 International Society for Neurochemistry, J. Neurochem. (2007) 101, 1161-1171
  4. [95]95. 5-HT and neuronal growth factor signaling pathways 1171 Ó 2007 The Author Journal Compilation Ó 2007 International Society for Neurochemistry, J. Neurochem. (2007) 101, 1161-1171 14714159, 2007, 5,

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Authors
Cowen, D. S.
Affiliations
University of Medicine and Dentistry of New Jersey (US)
Corresponding author
Cowen, Daniel S.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2007-02-05
Volume
101
Issue
5
Pages
1161-1171
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/j.1471-4159.2006.04420.x
OpenAlex
W2165564028
Cited by
72
References
91
Citations by year
2026: 2 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 3 · 2013: 8 · 2012: 1
FWCI
0.65
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (MH 60100, R01MH060100)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
serotonin, serotonin receptors, neuronal growth factors, neurotrophins, ERK signaling, Akt signaling, antidepressants, hippocampal neuroprotection, neurogenesis, monoamines, long-term synaptic plasticity
MeSH terms
Animals, Nerve Growth Factors, Neuronal Plasticity, Neurons, Serotonin, Signal Transduction

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