Reelin as a putative vulnerability factor for depression: examining the depressogenic effects of repeated corticosterone in heterozygous reeler mice.
We examined a potential two-hit murine animal model of depression by assessing whether a genetic deficit in reelin increases vulnerability to the depressogenic effects of the stress hormone corticosterone. Stress is an identified risk factor for the onset of depressive symptoms, but depression also has a significant genetic component, suggesting that environmental factors and genetic background likely interact in the etiology of depression. Previous results have revealed that reelin levels are decreased in post-mortem hippocampal tissue from patients with schizophrenia, bipolar disorder and depression, and also in an animal model of depression. Therefore, we hypothesized that heterozygous reeler mice (HRM), with approximately 50% normal levels of reelin, would be more sensitive to the depressogenic effects of corticosterone than wild-type mice (WTM). Mice received subcutaneous injections of either vehicle or 5 mg/kg, 10 mg/kg, or 20 mg/kg of corticosterone for 21 consecutive days, and then they were assessed for changes in depression-like behavior, hippocampal reelin expression, and hippocampal neurogenesis. Corticosterone produced dose-dependent increases in depression-like behavior and decreases in reelin expression, neurogenesis, and cell maturation regardless of mouse genotype. There were no differences between the vehicle-injected HRM and WTM in these measures. However, the effects of CORT on behavior, the number of reelin-positive cells in the subgranular zone or hilus, and hippocampal neurogenesis were more pronounced in the HRM than in the WTM, providing support for the idea that mice with impaired reelin signaling may be more vulnerable to the deleterious effects of glucocorticoids. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
Lussier
April L
AL
Neural Systems and Plasticity Research Group, Department of Psychology, University of Saskatchewan, Saskatoon, Saskatchewan S7V1C2, Canada.
Romay-Tallón
Raquel
R
Kalynchuk
Lisa E
LE
Caruncho
Hector J
HJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D015816:Cell Adhesion Molecules, Neuronal / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects; D003863:Depression / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D004334:Drug Administration Schedule; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006579:Heterozygote; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects; D009479:Neuropeptides / Q000187:drug effects / Q000502:physiology; D000091042:Reelin Protein; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology; D013550:Swimming
D000893:Anti-Inflammatory Agents; D015816:Cell Adhesion Molecules, Neuronal; D000089622:Doublecortin Domain Proteins; D016326:Extracellular Matrix Proteins; D005938:Glucocorticoids; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D003345:Corticosterone