title: Imipramine protects against the deleterious effects of chronic corticosterone on depression-like behavior, hippocampal reelin expression, and neuronal maturation.
abstract: We have hypothesized that a downregulation of reelin and deficient maturation of adult-born hippocampal neurons are important factors in the pathogenesis of depression. This hypothesis is based on previous work showing that depression-like behavior in rats treated with protracted corticosterone develops in concert with decreased dendritic complexity in newborn hippocampal granule neurons and decreased reelin expression in the proliferative subgranular zone of the dentate gyrus. In addition, heterozygous reeler mice with approximately 50% of normal brain levels of reelin are more vulnerable to the depressogenic effects of corticosterone than wild-type mice. The purpose of this experiment was to provide pharmacological validation for the link between reelin, neuronal maturation, and depression by examining whether the deleterious effects of corticosterone on these measures could be prevented by co-administration of the antidepressant imipramine. Rats received corticosterone injections, corticosterone injections plus either 10 or 15mg/kg imipramine injections, or vehicle injections for 21 consecutive days. They were then subjected to the forced swim test to assess depression-like behavior and sacrificed for immunohistochemical examination of immature neuron number and dendritic complexity and the presence of reelin+cells. We found that corticosterone increases depression-like behavior, decreases the number of reelin+cells in the subgranular zone, and decreases the number and complexity of immature neurons in the granule cell layer. All of these behavioral and cellular phenotypes were prevented by imipramine, providing further support for the idea that reelin is involved in the pathogenesis of depression.
authors: Division of Pharmacy, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors: Erin Y
authors: EY
authors: Fenton
authors: Department of Psychology, Trent University, Peterborough, Ontario, Canada.
authors: Neil M
authors: NM
authors: Fournier
authors: Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors: April L
authors: AL
authors: Lussier
authors: Division of Pharmacy, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors: Raquel
authors: R
authors: Romay-Tallon
authors: Division of Pharmacy, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors: Hector J
authors: HJ
authors: Caruncho
authors: Division of Neurology, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. Electronic address: lisa.kalynchuk@usask.ca.
authors: Lisa E
authors: LE
authors: Kalynchuk
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D003345:Corticosterone / Q000633:toxicity*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003863:Depression / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007099:Imipramine / Q000494:pharmacology*; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013550:Swimming / Q000523:psychology
chemical_list: D000893:Anti-Inflammatory Agents; D000929:Antidepressive Agents, Tricyclic; D015816:Cell Adhesion Molecules, Neuronal; D000089622:Doublecortin Domain Proteins; D016326:Extracellular Matrix Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000091042:Reelin Protein; C000717129:Reln protein, rat; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D007099:Imipramine; D003345:Corticosterone
keywords: Antidepressant; Corticosterone; Depression; Neurogenesis; Reelin