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Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone
M J Schaaf1, J de Jong, E R de Kloet
1Leiden/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
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.
Insights
Corticosterone transiently decreases brain-derived neurotrophic factor (BDNF) mRNA and protein in the hippocampus. This dose-dependent effect, observed in rodents, may influence hippocampal neuronal plasticity following acute stress.
Area of Science:
- Neuroscience
- Molecular Biology
- Endocrinology
Background:
- Corticosterone is known to regulate hippocampal BDNF mRNA levels.
- Previous studies established a link between corticosterone and BDNF regulation.
Purpose of the Study:
- To investigate the time course and dose-dependency of corticosterone's effect on BDNF at both mRNA and protein levels.
- To examine the impact of corticosterone on trkB mRNA levels in the hippocampus.
Main Methods:
- Adrenalectomized rodents received subcutaneous corticosterone (30 and 1000 µg/kg).
- BDNF and trkB mRNA levels were measured using in situ hybridization at 3, 6, 12, and 24 hours.
- BDNF protein levels were assessed via ELISA at 4 and 6 hours post-administration.
Main Results:
- A dose-dependent decrease in BDNF mRNA was observed in the dentate gyrus and CA1 region at 3 hours.
- High-dose corticosterone reduced BDNF mRNA by 70% (dentate gyrus) and 40% (CA1).
- BDNF protein decreased by 17% at 4 hours and 14% at 6 hours after high-dose corticosterone.
- TrkB mRNA levels were initially unaffected but increased between 6 and 24 hours.
Conclusions:
- Corticosterone induces a transient, dose-dependent downregulation of hippocampal BDNF mRNA and protein.
- These findings suggest a mechanism by which short-term changes in corticosterone influence hippocampal neuronal plasticity.