title: Creatine Prevents Corticosterone-Induced Reduction in Hippocampal Proliferation and Differentiation: Possible Implication for Its Antidepressant Effect.
abstract: The benefits of creatine supplementation have been reported in a broad range of central nervous system diseases, including depression, although the mechanisms underlying these effects remain to be understood. In the present study, we investigated the ability of creatine to counteract the morphological and behavioral effects elicited by chronic administration of corticosterone (CORT, 20 mg/kg, p.o.) for 21 days to mice, a pharmacological model of depression that mimics exposure to stress. CORT treatment increased immobility time in the tail suspension test (TST) and forced swim test (FST), as well as latency to immobility in the FST, and decreased the sucrose consumption in the sucrose preference test (SPT). These behavioral effects were associated with decreased hippocampal cell proliferation and neuronal differentiation and increased glial fibrillary acid protein (GFAP) immunostaining (suggestive of astrogliosis) in dentate gyrus (DG) of the hippocampus. These CORT-induced alterations were abolished by treatment with either fluoxetine (a conventional antidepressant) or creatine for 21 days (both 10 mg/kg, p.o.). In addition, fluoxetine, but not creatine, was able to reverse the CORT-induced reduction in serum CORT levels. Collectively, our results suggest that creatine produces morphological alterations that contribute to the improvement of depressive-like behaviors triggered by chronic CORT administration in mice.
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Francis L
authors.initials: FL
authors.lastname: Pazini
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Mauricio P
authors.initials: MP
authors.lastname: Cunha
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Dayane
authors.initials: D
authors.lastname: Azevedo
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Rosa
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Colla
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Jade
authors.initials: J
authors.lastname: de Oliveira
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Ramos-Hryb
authors.affiliation: Department of Morphological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Brocardo
authors.affiliation: Division of Medical Sciences and UBC Island Medical Program, University of Victoria, 3800 Finnerty Road, Victoria, BC, V8P 5C2, Canada.
authors.forename: Joana
authors.initials: J
authors.lastname: Gil-Mohapel
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil. alsrodri@gmail.com.
authors.forename: Ana Lúcia S
authors.initials: ALS
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003345:Corticosterone / Q000494:pharmacology*; D003401:Creatine / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013395:Sucrose
chemical_list: D000928:Antidepressive Agents; D005904:Glial Fibrillary Acidic Protein; C528900:glial fibrillary astrocytic protein, mouse; D005473:Fluoxetine; D013395:Sucrose; D003401:Creatine; D003345:Corticosterone
keywords: Adult neurogenesis; Cell proliferation; Corticosterone; Creatine; Depression; Hippocampus; Neuronal differentiation