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Molecular Neurobiology

, Volume 48, Issue 1, pp 244–256 | Cite as

Lack of Serotonin Transporter Alters BDNF Expression in the Rat Brain During Early Postnatal Development

  • Francesca Calabrese
  • Gianluigi Guidotti
  • Anthonieke Middelman
  • Giorgio Racagni
  • Judith Homberg
  • Marco A. Riva
Article

Abstract

It is well established that alterations of the serotoninergic system may contribute to the pathophysiology of mood disorders. Accordingly, it has been demonstrated that genetic deletion of the serotonin transporter (SERT) in rodents leads to an anxious and depressive phenotype, which is also associated with reduced neuronal plasticity. Indeed, we have demonstrated that adult SERT−/− animals show decreased brain-derived neurotrophic factor (BDNF) expression, as well as reduced levels of transcription factor regulating the neurotrophin transcription. While these changes may represent long-term consequences of impaired function of the transporter during development, no information exists with respect to the developmental profile of such changes. Using SERT−/− rats at different ages, we found that the impairment in neuroplasticity originates early in development and worsens during the first 3 weeks of life. Indeed, we observed that BDNF expression was reduced at birth and that the magnitude of these changes became more pronounced starting from PND21, being sustained by epigenetic mechanisms as well as alterations in the expression of specific transcription factors, including Npas4 and CaRF. These results suggest that an impairment of SERT may affect BDNF expression throughout postnatal development. These early changes may increase stress susceptibility during critical windows of brain maturation, which may eventually lead to the heightened predisposition to mood disorders found in individual carrying genetic variants of the serotonin transporter.

Keywords

Transcription factors Epigenetic mechanisms Neuroplasticity Psychiatric disorders Depression 

Notes

Acknowledgments

This publication was made possible by grants to M.A. Riva from Regione Lombardia (Markdep) and from an European Research Projects on Mental Disorders (ERA-NET NEURON 2010), as well as by grants from The Netherlands Organisation for Scientific Research (NWO, grant # 86410003), to J. Homberg.

Conflict of Interest

The authors Calabrese F, Guidotti G, Middelman A, and Homberg J have no financial interest or potential conflict of interest. Racagni G has received compensation as speaker/consultant for Eli Lilly, InnovaPharma, Roche, Servier. Riva MA has received compensation as speaker/consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Roche, Servier, Takeda.

Supplementary material

12035_2013_8449_MOESM1_ESM.doc (154 kb)
ESM 1 (DOC 153 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Francesca Calabrese
    • 1
  • Gianluigi Guidotti
    • 1
  • Anthonieke Middelman
    • 3
  • Giorgio Racagni
    • 1
    • 2
    • 5
  • Judith Homberg
    • 3
  • Marco A. Riva
    • 1
    • 2
    • 4
  1. 1.Dipartimento di Scienze Farmacologiche e BiomolecolariUniversita’ degli Studi di MilanoMilanItaly
  2. 2.Center of Excellence on Neurodegenerative DiseasesUniversità degli Studi di MilanoMilanItaly
  3. 3.Donders Institute for Brain, Cognition, and Behaviour, Department of Cognitive NeuroscienceRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  4. 4.Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly
  5. 5.I.R.C.C.S. San Giovanni di Dio-FatebenefratelliBresciaItaly

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