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Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
Author(s) -
Diaz Silvina L.,
NarbouxNême Nicolas,
Trowbridge Sara,
ScottoLomassese Sophie,
Kleine Borgmann Felix B.,
Jessberger Sebastian,
Giros Bruno,
Maroteaux Luc,
Deneris Evan,
Gaspar Patricia
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12297
Subject(s) - dentate gyrus , neurogenesis , subgranular zone , hippocampal formation , serotonergic , serotonin , hippocampus , neuroscience , 5 ht receptor , endocrinology , neural stem cell , medicine , receptor , biology , microbiology and biotechnology , subventricular zone , stem cell
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 ; SERT cre/+ 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‐ HT 1A 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‐ HT 1A receptors. The role of 5‐ HT in selective neuronal elimination points to a new facet in its multiple effects in controlling neural circuit maturation.