title: Ziprasidone--not haloperidol--induces more de-novo neurogenesis of adult neural stem cells derived from murine hippocampus.
abstract: BACKGROUND
  Here, we present a stem-cell based study on the de-novo generation of beta-III-tubulin-positive neurons after treatment with the classic antipsychotic drug haloperidol or after treatment with the second-generation antipsychotic (SGA) ziprasidone.
  
  
  METHODS
  Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in cell culture with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). ANSC differentiated upon withdrawal of EGF and bFGF.
  
  
  CONCLUSIONS
  Ziprasidone generated significantly more beta-III-tubulin-positive neurons than haloperidol during the differentiation of adult neural stem cells isolated from murine hippocampus (ANSC). We assume that this net increase in neurogenesis by ziprasidone relies on this drug's 5-HT1A receptor affinity, which is not present in the haloperidol molecule, since the inactivation by WAY100621 impeded this process. These data could possibly suggest a clinical relevance for studying antipsychotic drugs in the stem cell paradigm employed in this study.
authors.affiliation: Department of Psychiatry, LMU-University of Munich, Munich, Germany. jens.benninghoff @lvr.de
authors.forename: J
authors.initials: J
authors.lastname: Benninghoff
authors.forename: H
authors.initials: H
authors.lastname: Grunze
authors.forename: C
authors.initials: C
authors.lastname: Schindler
authors.forename: J
authors.initials: J
authors.lastname: Genius
authors.forename: R J
authors.initials: RJ
authors.lastname: Schloesser
authors.forename: A
authors.initials: A
authors.lastname: van der Ven
authors.forename: S
authors.initials: S
authors.lastname: Dehning
authors.forename: J
authors.initials: J
authors.lastname: Wiltfang
authors.forename: H J
authors.initials: HJ
authors.lastname: Möller
authors.forename: D
authors.initials: D
authors.lastname: Rujescu
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D014404:Tubulin / Q000096:biosynthesis
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D012702:Serotonin Antagonists; D013844:Thiazoles; D014404:Tubulin; D016222:Fibroblast Growth Factor 2; D044282:Receptor, Serotonin, 5-HT1A; D004815:Epidermal Growth Factor; C092292:ziprasidone; D006220:Haloperidol