Chronic corticosterone decreases brain-derived neurotrophic factor (BDNF) mRNA and protein in the hippocampus, but not in the frontal cortex, of the rat.
This study examined the effects of chronic corticosterone (32 mg/kg/day, s.c., 21 days) on brain-derived neurotrophic factor (BDNF) mRNA and protein in the frontal cortex and hippocampus of the rat. Because evidence suggests that BDNF is an important determinant of the function of the 5-hydroxytryptamine (5-HT) system, we also quantified tissue levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), to investigate if changes in BDNF mRNA and protein paralleled changes in the 5-HT system. Corticosterone modestly decreased BDNF protein (-16.6%) in whole hippocampus and BDNF mRNA (-19%) in the CA3 area. In contrast, BDNF mRNA and protein in the frontal cortex were unchanged. In both the frontal cortex and hippocampus, tissue levels of 5-HT and 5-HIAA were increased and decreased, respectively. Combined, these data suggests that the effects of corticosterone on the BDNF system are not linked to the effects on the 5-HT systems. However, our findings do suggest that chronic corticosterone impairs hippocampal BDNF function, a finding with potential relevance for the hippocampal atrophy reported in major depression. Additionally, as inferred from the alterations in tissue levels of 5-HT and 5-HIAA, chronic corticosterone may influence the function of the 5-HT system.
Jacobsen
Jacob P R
JP
Department of In Vivo Pharmacology, NeuroSearch A/S, Pederstrupvej 93, Ballerup, Denmark. jpj@neurosearch.dk
Mørk
Arne
A
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001923:Brain Chemistry / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005625:Frontal Lobe / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003345:Corticosterone