title: Reelin-Related Disturbances in Depression: Implications for Translational Studies.
abstract: The finding that reelin expression is significantly decreased in mood and psychotic disorders, together with evidence that reelin can regulate key aspects of hippocampal plasticity in the adult brain, brought our research group and others to study the possible role of reelin in the pathogenesis of depression. This review describes recent progress on this topic using an animal model of depression that makes use of repeated corticosterone (CORT) injections. This methodology produces depression-like symptoms in both rats and mice that are reversed by antidepressant treatment. We have reported that CORT causes a decrease in the number of reelin-immunopositive cells in the dentate gyrus subgranular zone (SGZ), where adult hippocampal neurogenesis takes place; that down-regulation of the number of reelin-positive cells closely parallels the development of a depression-like phenotype during repeated CORT treatment; that reelin downregulation alters the co-expression of reelin with neuronal nitric oxide synthase (nNOS); that deficits in reelin might also create imbalances in glutamatergic and GABAergic circuits within the hippocampus and other limbic structures; and that co-treatment with antidepressant drugs prevents both reelin deficits and the development of a depression-like phenotype. We also observed alterations in the pattern of membrane protein clustering in peripheral lymphocytes in animals with low levels of reelin. Importantly, we found parallel changes in membrane protein clustering in depression patients, which differentiated two subpopulations of naïve depression patients that showed a different therapeutic response to antidepressant treatment. Here, we review these findings and develop the hypothesis that restoring reelin-related function could represent a novel approach for antidepressant therapies.
authors.affiliation: Neuroscience Cluster, College of Pharmacy and Nutrition, University of Saskatchewan Saskatoon, SK, Canada.
authors.forename: Hector J
authors.initials: HJ
authors.lastname: Caruncho
authors.affiliation: Department of Psychology, University of Saskatchewan Saskatoon, SK, Canada.
authors.forename: Kyle
authors.initials: K
authors.lastname: Brymer
authors.affiliation: Department of Medicine, University of Saskatchewan Saskatoon, SK, Canada.
authors.forename: Raquel
authors.initials: R
authors.lastname: Romay-Tallón
authors.affiliation: Department of Psychology, University of Saskatchewan Saskatoon, SK, Canada.
authors.forename: Milann A
authors.initials: MA
authors.lastname: Mitchell
authors.affiliation: Department of Psychiatry, Alvaro Cunqueiro Hospital, Biomedical Research Institute of Vigo Galicia, Spain.
authors.forename: Tania
authors.initials: T
authors.lastname: Rivera-Baltanás
authors.affiliation: Department of Psychology, University of Saskatchewan Saskatoon, SK, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Botterill
authors.affiliation: Department of Psychiatry, Alvaro Cunqueiro Hospital, Biomedical Research Institute of Vigo Galicia, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Olivares
authors.affiliation: Department of Medicine, University of Saskatchewan Saskatoon, SK, Canada.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Kalynchuk
keywords: depression; hippocampus; lymphocytes; membrane protein clustering; neural plasticity; neurogenesis; reelin