Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
Open accessAbstract
Increased adult neurogenesis is a major neurobiological correlate of the beneficial effects of antidepressants. Indeed, selective serotonin (5‐HT) re‐uptake inhibitors, which increase 5‐HT transmission, enhance adult neurogenesis in the dentate gyrus (DG) of the hippocampus. However, the consequences of 5‐HT depletion are still unclear as studies using neurotoxins that target serotonergic neurons reached contradictory conclusions on the role of 5‐HT on DG cell proliferation. Here, we analysed two genetic models of 5‐HT depletion, the Pet1−/− and the VMAT 2 f/f; SERTcre/+ mice, which have, respectively, 80 and 95% reductions in hippocampal 5‐HT. In both models, we found unchanged cell proliferation of the neural precursors in the DG subgranular zone, whereas a significant increase in the survival of newborn neurons was noted 1 and 4 weeks after BrdU injections. This pro‐survival trait was phenocopied pharmacologically with 5‐HT synthesis inhibitor PCPA treatment in adults, indicating that this effect was not developmental. Furthermore, a 1‐week administration of the 5‐HT1A receptor agonist 8‐OH‐DPAT in Pet1−/− and PCPA‐treated mice normalised hippocampal cell survival. Overall, our results indicate that constitutive 5‐HT depletion does not alter the proliferation of neural precursors in the DG but promotes the survival of newborn cells, an effect which involves activation of postsynaptic 5‐HT1A receptors. The role of 5‐HT in selective neuronal elimination points to a new facet in its multiple effects in controlling neural circuit maturation.
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Neuronal proliferation occurs at a normal rate upon complete depletion or dramatic reduction of 5-HT in Tph2 deficient mice and two other genetic mice models.
“Surprisingly, neuronal proliferation occurs at a normal rate upon complete depletion or dramatic reduction of 5-HT in Tph2 deficient mice and two other genetic mice models (Diaz et al., 2013;Klempin et al., 2013).”
From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Diaz et al., 2013
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- Authors
- Diaz, S. L., Narboux‐Nême, N., Trowbridge, S., Scotto‐Lomassese, S., Kleine Borgmann, F. B., Jessberger, S., Giros, B., Maroteaux, L., Deneris, E., & Gaspar, P.
- Affiliations
- Inserm (FR)
- Brain Research Institute University of Zurich Zurich Switzerland
- University of Zurich (CH)
- UPMC Paris France
- Case Western Reserve University (US)
- Inserm, UMR‐S 839 France
- ORCID
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2013-07-10
- Volume
- 38
- Issue
- 5
- Pages
- 2650-2658
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2121530458
- Cited by
- 41
- References
- 45
- Citations by year
- 2026: 1 · 2025: 2 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 8 · 2016: 8 · 2015: 3 · 2014: 5 · 2013: 2
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Université Pierre et Marie CURIE (UPMC) (submittedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Harvard University
- European Commission (201714)
- Agence Nationale de la Recherche (ANR-08-MNPS-0032)
- Institut National de la Santé et de la Recherche Médicale
- Université Pierre et Marie Curie
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- serotonin depletion, adult neurogenesis, dentate gyrus, newborn neuron survival, 5-HT1A receptor, 8-OH-DPAT, p-chlorophenylalanine, vesicular monoamine transporter 2, serotonin transporter, neural precursor proliferation, subgranular zone, hippocampus, antidepressants, selective serotonin reuptake inhibitors
- MeSH terms
- Animals, Cell Survival, Female, Male, Mice, Inbred C57BL, Neurons, Fenclonine, Receptors, Serotonin, Serotonin, Serotonin Antagonists, Mice, Knockout, Dentate Gyrus, Vesicular Monoamine Transport Proteins, Mice, Neurogenesis
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