Effects of corticosterone on the expression of mature brain-derived neurotrophic factor (mBDNF) and proBDNF in the hippocampal dentate gyrus

Chronic stressor induces the release of glucocorticoid from the adrenal glands, the subsequent decrease of hippocampal volume, and the development of depression. Brain-derived neurotrophic factor (BDNF), composed of mature BDNF (mBDNF) and proBDNF, plays opposite roles in the structural integrity of the brain. However, the underlying mechanism of glucocorticoid-induced hippocampal atrophy remains unclear. Using the open field test, sucrose preference test, elevated plus maze test, and forced swimming test, we observed that the chronic (3 w) administration of corticosterone (CORT) (50 μg/ml) induced depressive-like behaviors in rats. Next, using Western blot assay, we showed that CORT exposure increased the proBDNF level in the ventral hippocampal dentate gyrus (DG), decreased the mBDNF level in the dorsal and ventral DG, and decreased the mBDNF/proBDNF ratio in the hippocampal DG. Furthermore, CORT administration differentially altered the expression of 11 Bdnf mRNA transcripts in the dorsal and ventral hippocampal DG. Our findings suggest an essential role for the mBDNF-proBDNF system in regulating the hippocampus of CORT-treated rats and present a new therapeutic mechanism for antidepressant treatments by targeting the Bdnf mRNA transcripts.