The Long-Term Effects of Ethanol and Corticosterone on the Mood-Related Behaviours and the Balance Between Mature BDNF and proBDNF in Mice.

ABSTRACT

In this study, we aimed to establish the effects of chronic corticosterone (CORT) and ethanol administration on mood-related behaviour and the levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor protein proBDNF in mice. C57BL6 male and female mice received drinking water (n = 22), 1% ethanol in drinking water (n = 16) or 100 µg/ml corticosterone in drinking water (containing 1% ethanol, n = 18) for 4.5 weeks. At the end of experimental protocol, the open field test (OFT) and elevated plus maze test were performed. Brain and adrenal tissues were collected and mBDNF and proBDNF were measured by ELISA assays. We found that the mice fed with corticosterone and ethanol developed anxiety-like behaviours as evidenced by reduced time in the central zone in the OFT compared with the control group. Both proBDNF and mBDNF were significantly decreased in the corticosterone and ethanol groups compared with the control group in the prefrontal cortex, hippocampus, hypothalamus and adrenal. The ratio of proBDNF/mBDNF in prefrontal cortex in the corticosterone group was increased compared with the ethanol group. Our data suggest that the ratio of proBDNF/mBDNF is differentially regulated in different tissues. Ethanol and corticosterone downregulate both mBDNF and proBDNF and alter the balance of proBDNF/mBDNF in some tissues. In conclusion, the ethanol and corticosterone may cause abnormal regulation of mBDNF and proBDNF which may lead to mood disorders.