Adult neurogenesis in serotonin transporter deficient mice

A. Schmitt, J. Benninghoff, R. Moessner, M. Rizzi, E. Paizanis, C. Doenitz, S. Gross, M. Hermann, A. Gritti, L. Lanfumey, S. Fritzen, A. Reif, M. Hamon, D. L. Murphy, A. Vescovi, K. P. Lesch

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Serotonin (5-HT) is a regulator of morphogenetic activities during early brain development and neurogenesis, including cell proliferation, migration, differentiation, and synaptogenesis. The 5-HT transporter (5-HTT, SLC6A4) mediates high-affinity reuptake of 5-HT into presynaptic terminals and thereby fine-tunes serotonergic neurotransmission. Inactivation of the 5-HTT gene in mice reduces 5-HT clearance resulting in persistently increased concentrations of synaptic 5-HT. In the present study, we investigated the effects of elevated 5-HT levels on adult neurogenesis in the hippocampus of 5-HTT deficient mice, including stem cell proliferation, survival, and differentiation. Using an in vivo approach, we showed an increase in proliferative capacity of hippocampal adult neural stem cells in aged 5-HTT knockout mice (∼14.5 months) compared to wildtype controls. In contrast, in vivo and additional in vitro analyses of younger adult 5-HTT knockout mice (∼7 weeks and ∼3.0 months) did not reveal significant changes in proliferation of neural stem cells or survival of newborn cells. We showed that the cellular fate of newly generated cells in 5-HTT knockout mice is not different with respect to the total number and percentage of neurons or glial cells from wildtype controls. Our findings indicate that elevated synaptic 5-HT concentration throughout early development and later life of 5-HTT deficient mice does not induce adult neurogenesis in adult mice, but that elevated 5-HT levels in aged mice influence stem cell proliferation.

Original languageEnglish (US)
Pages (from-to)1107-1119
Number of pages13
JournalJournal of Neural Transmission
Volume114
Issue number9
DOIs
StatePublished - Sep 2007

Keywords

  • Adult neurogenesis
  • Aging
  • Anxiety
  • Depression
  • Knockout
  • Serotonin transporter

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Fingerprint Dive into the research topics of 'Adult neurogenesis in serotonin transporter deficient mice'. Together they form a unique fingerprint.

Cite this