title: Imipramine enhances cell proliferation and decreases neurodegeneration in the hippocampus after transient global cerebral ischemia in rats.
abstract: This study was aimed to determine whether imipramine chronic treatment promotes neurogenesis in the dentate gyrus (DG) and interferes with neuronal death in the CA1 subfield of the hippocampus after transient global cerebral ischemia (TGCI) in rats. After TGCI, animals were treated with imipramine (20mg/kg, i.p.) or saline during 14 days. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) was injected 24h after the last imipramine or saline injection to label proliferating cells. In order to confirm the effect of TGCI on neuronal death and cell proliferation, a group of animals was sacrificed 7 days after TGCI. Neurogenesis and neurodegeneration were evaluated by doublecortin (DCX)-immunohistochemistry and Fluoro-Jade C (FJC)-staining, respectively. The rate of cell proliferation increases 7 days but returns to basal levels 14 days after TGCI. There was a significant increase in the number of FJC-positive neurons in the CA1 of animals 7 and 14 days after TGCI. Chronic imipramine treatment increased cell proliferation in the SGZ of DG and reduced the neurodegeneration in the CA1 of the hippocampus 14 days after TGCI. Immunohistochemistry for DCX detected an increased number of newly generated neurons in the hippocampal DG 14 days after TGCI, which was not affected by imipramine treatment. Further studies are needed to evaluate whether imipramine treatment for longer time would be able to promote survival of newly generated neurons as well as to improve functional recovery after TGCI.
authors.affiliation: Department of Pharmacology, State University of Maringá, Av. Colombo 5790, 87020-900 Maringá, PR, Brazil.
authors.forename: Angélica P
authors.initials: AP
authors.lastname: Schiavon
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
authors.forename: Cássia V
authors.initials: CV
authors.lastname: Romanini
authors.forename: Maira Licia
authors.initials: ML
authors.lastname: Foresti
authors.forename: Olagide W
authors.initials: OW
authors.lastname: Castro
authors.forename: Norberto
authors.initials: N
authors.lastname: Garcia-Cairasco
authors.forename: Rúbia M W
authors.initials: RM
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy*; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D055153:Stem Cell Niche / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; D007099:Imipramine