title: Regional-specific effect of fluoxetine on rapidly dividing progenitors along the dorsoventral axis of the hippocampus.
abstract: Hippocampus-dependent cognitive and emotional function appears to be regionally dissociated along the dorsoventral (DV) axis of the hippocampus. Recent observations that adult hippocampal neurogenesis plays a critical role in both cognition and emotion raised an interesting question whether adult neurogenesis within specific subregions of the hippocampus contributes to these distinct functions. We examined the regional-specific and cell type-specific effects of fluoxetine, which requires adult hippocampal neurogenesis to function as an antidepressant, on the proliferation of hippocampal neural stem cells (NSCs). Fluoxetine specifically increased proliferation of NSCs located in the ventral region of the hippocampus while the mitotic index of NSCs in the dorsal portion of the hippocampus remained unaltered. Moreover, within the ventral hippocampus, type II NSC and neuroblast populations specifically responded to fluoxetine, showing increased proliferation; however, proliferation of type I NSCs was unchanged in response to fluoxetine. Activation or inhibition of serotonin receptor 1A (5-HTR1A) recapitulated or abolished the effect of fluoxetine on proliferation of type II NSCs and neuroblast populations in the ventral hippocampus. Our study showed that the effect of fluoxetine on proliferation is dependent upon the type and the position of the NSCs along the DV axis of the hippocampus.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.|Institution of Stem Cells and Neuroregeneration, Department of Pharmacology, Pharmacy College, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Qi-Gang
authors.initials: QG
authors.lastname: Zhou
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Daehoon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Eun Jeoung
authors.initials: EJ
authors.lastname: Ro
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Hoonkyo
authors.initials: H
authors.lastname: Suh
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003071:Cognition; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects* / Q000473:pathology; D055495:Neurogenesis; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; C583518:HTR1A protein, human; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A