Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone.
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.
Schaaf
M J
MJ
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
de Jong
J
J
de Kloet
E R
ER
Vreugdenhil
E
E
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
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