title: Partial serotonergic denervation decreases progenitor cell proliferation in the adult rat hippocampus, but has no effect on rat behavior in the forced swimming test.
abstract: It has been hypothesized that impaired serotonin (5-HT) neurotransmission contributes to the pathophysiology of depression. Recently, it was shown in adult animals that antidepressants which influence 5-HT levels increase hippocampal progenitor cell proliferation, suggesting an important role of the 5-HT system in the regulation of adult neurogenesis. In this study, we investigated the effects of partial 5-HT denervation of the adult rat forebrain caused by a single para-chloroamphetamine (PCA) administration (10 mg/kg, s.c.) on hippocampal progenitor cell proliferation measured by Ki-67 immunohistochemistry over a 3-week time period. Moreover, behavior of rats was analyzed by using the forced swimming test which serves as a so-called animal model of depression. One week after PCA administration, a significant decrease of Ki-67 immunopositive cells and cell clusters (-25% and -53%, respectively) was found which was recovered over the 3-week period. The decrease in progenitor cell proliferation in the dentate gyrus per animal was positively correlated with the 5-HT denervation. Behavioral analysis of rats revealed no significant differences between vehicle and PCA-treated animals at any of the examined time points. These findings indicate a regulative role of 5-HT for hippocampal progenitor cell proliferation and neurogenesis, but its relation to animal models of depression remains to be elucidated.
authors.affiliation: Department of CNS Research, Boehringer-Ingelheim Pharma GmbH and Co KG, D-88397 Biberach, Germany. holger.rosenbrock@bc.boehringer-ingelheim.com
authors.forename: Holger
authors.initials: H
authors.lastname: Rosenbrock
authors.forename: Anita
authors.initials: A
authors.lastname: Bloching
authors.forename: Carmen
authors.initials: C
authors.lastname: Weiss
authors.forename: Franco
authors.initials: F
authors.lastname: Borsini
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D002452:Cell Count; D049109:Cell Proliferation; D003714:Denervation; D003863:Depression / Q000523:psychology*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins; D013234:Stem Cells / Q000502:physiology*; D013550:Swimming / Q000523:psychology; D010133:p-Chloroamphetamine / Q000494:pharmacology
chemical_list: D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D010133:p-Chloroamphetamine