title: Prednisolone causes anxiety- and depression-like behaviors and altered expression of apoptotic genes in mice hippocampus.
abstract: Glucocorticoids are known to cause psychiatric disorders including depression. Prednisolone (PSL) is one of the most widely used synthetic glucocorticoids to treat various medical diseases; however, little is known about PSL-induced behavioral changes and its molecular basis in the brain. Growing evidence has implicated that hippocampal remodeling or damage play a role in the pathogenic effect of glucocorticoids. In this study, mice were administered PSL (50 or 100mg/kg) or vehicle for 6 or 7 days and subjected to a series of behavioral tests, i.e., open field, elevated plus maze, prepulse inhibition, forced swim, and tail suspension tests. Hippocampal tissues were subject to microarray analysis using the GeneChip Mouse Genome 430 2.0 Array (Affymetrix) containing 45,101 probes of transcripts. Increased anxiety- and depression-like behaviors assessed with open field, elevated plus maze, and tail suspension tests were observed. Microarray analysis detected 108 transcripts with a fold change of >2.0 or <0.5 in which many cell-death-related genes were found. The microarray data was validated by quantitative reverse transcriptase-polymerase chain reaction analysis. Our results demonstrated that PSL causes anxiety- and depression-like behaviors, and suggest that altered gene expressions related to hippocampal remodeling or damage are involved in the effect of PSL on such behaviors.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kajiyama
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iijima
authors.forename: Shuichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Miyako
authors.initials: M
authors.lastname: Furuta
authors.forename: Midori
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Aiko
authors.initials: A
authors.lastname: Izumi
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Shibata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D003863:Depression / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D019417:Hindlimb Suspension / Q000379:methods; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011239:Prednisolone / Q000494:pharmacology; D013216:Reflex, Startle / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013550:Swimming / Q000523:psychology
chemical_list: D011239:Prednisolone