title: Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone.
abstract: Previously, we showed that corticosterone regulates BDNF mRNA levels in the hippocampus. In the present study, we have investigated the time course and dose-dependency of this effect at both the mRNA and the protein level. Corticosterone was administered in doses of 30 and 1000 microgram/kg b.w. subcutaneously to adrenalectomized animals. At 3, 6, 12 and 24 h after administration BDNF and trkB mRNA levels in hippocampal subfields were measured by in situ hybridization. Our results show a dose-dependent decrease in BDNF mRNA in dentate gyrus and CA1 at 3 h. After the high dose, this decrease was 70% and 40% respectively. In addition, ELISA was performed to study if this downregulation is also detectable at the protein level. Hippocampal tissue was used from adrenalectomized animals which had received 1000 microgram/kg b.w. corticosterone 4 and 6 h before decapitation. At both time points, a decrease in BDNF protein was observed; 17% at 4 h and 14% at 6 h after corticosterone, as compared to the vehicle injected controls. TrkB mRNA levels were not affected by corticosterone. However, between 6 and 24 h after treatment, increases in trkB mRNA were observed. In conclusion, we have found a transient, dose-dependent decrease in BDNF mRNA and protein in the hippocampus, which may underly changes in neuronal plasticity in the hippocampus after short-term changes in corticosterone concentrations.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Division of Medical Pharmacology, Sylvius Laboratories, P.O. Box 9503, 2300 RA, Leiden, The Netherlands. m.schaaf@lacdr.leidenuniv.nl
authors.forename: M J
authors.initials: MJ
authors.lastname: Schaaf
authors.forename: J
authors.initials: J
authors.lastname: de Jong
authors.forename: E R
authors.initials: ER
authors.lastname: de Kloet
authors.forename: E
authors.initials: E
authors.lastname: Vreugdenhil
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D003345:Corticosterone