title: Chronic corticosterone manipulations in mice affect brain cell proliferation rates, but only partly affect BDNF protein levels.
abstract: We investigated whether the effects of corticosterone (CORT) on brain cell proliferation are mediated via its detrimental effect on brain-derived neurotrophic factor (BDNF). Using a [3H]thymidine tracer study, it was demonstrated that the cell proliferation rate in the neurogenic hippocampus and subventricular zone was increased in placebo-treated adrenalectomized (ADX) mice with low plasma corticosterone levels when compared with chronically CORT-treated ADX animals (25mg or 100mg sustained-release pellet). The cell proliferation rate of SHAM animals was in between the ADX-placebo group and ADX CORT-treated groups. BDNF protein contents in the hippocampus and subventricular zone were not different between the SHAM group and ADX-placebo group, although BDNF contents were decreased in the chronically CORT-treated ADX animals. Thus, other factors besides BDNF are involved in mediating CORT-induced changes in cell proliferation. Further, CORT manipulations did not affect caspase-3-like activity in any of the brain regions investigated, suggesting that caspase-3 is not involved in possible CORT-induced cellular losses.
authors.affiliation: Division of Psychiatry, Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium. jos.prickaerts@np.unimaas.nl
authors.forename: Jos
authors.initials: J
authors.lastname: Prickaerts
authors.forename: Daniël L A
authors.initials: DL
authors.lastname: van den Hove
authors.forename: Frederik L P
authors.initials: FL
authors.lastname: Fierens
authors.forename: Hossein K
authors.initials: HK
authors.lastname: Kia
authors.forename: Ilse
authors.initials: I
authors.lastname: Lenaerts
authors.forename: Thomas
authors.initials: T
authors.lastname: Steckler
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood* / Q000494:pharmacology; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020547:Lateral Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003345:Corticosterone