Effects of corticosterone on BDNF expression and mood behaviours in mice

Stress hormones such as cortisol play a critical role in depressive disorders. Therefore, corticosterone has been used to develop a depression model in animals. Our previous studies found that the precursor of brain-derived neurotrophic factor (proBDNF) and its receptors are upregulated in depression in human and animal models. In the present study, we aimed to examine whether proBDNF and mature BDNF (mBDNF) are altered in the corticosterone-induced depression model in mice. Male and female mice were given corticosterone dissolved in 0.3% hydroxypropyl- β-cyclodextrin (β-CD) or vehicle (β-CD) in drinking water for 33 days. We have found that corticosterone induced depressive-like behaviours as reflected by increased immobility time in the tail suspension test and decreased grooming time in the splash test. Corticosterone also induced anxiety-like behaviours as represented by decreased entries into the central zone of the open field test and the open arms of the elevated plus maze test. We found that corticosterone administration resulted in differential changes of proBDNF and mature BDNF in different brain regions and peripheral tissues. ProBDNF was increased in the hippocampus and cerebellum, but no change was found in the prefrontal cortex and hypothalamus. Both proBDNF and mBDNF were significantly increased in the pituitary gland. In contrast, proBDNF was significantly decreased in the adrenal gland.  There were no significant changes in proBDNF or mBDNF in other peripheral tissues, including the liver and sex organs. We conclude that the stress hormone corticosterone causes depressive behaviours but differentially regulates the processing of proBDNF in mice. ProBDNF may participate in the development of depression behaviours in corticosterone treated animals.