Effects Of Neonatal Stress Exposure On Bdnf Protein In Adolescent (Pnd 30) Mouse Brain

Abstract

Traumatic childhood experiences are a major risk factor for anxiety disorders and depression. Brain-derived neurotrophic factor (BDNF) is critical to the developing brain; reduced BDNF levels have been observed in these disorders. Studies show that early life stress programs the development of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in sustained activation of the HPA axis and behavioral changes. A link between elevated levels of corticosteroids (CORT), and decreased BDNF protein also has been observed. Thus, early life trauma and stress may contribute to functional changes in brain structure and neuroplasticity via alteration in BDNF protein levels. Our laboratory developed a model for short duration, early life, maternal separation (MS) stress using Balb/CByJ mice, employing a split-litter design, where half the pups were removed from their dam for 1 hr./day from PND 2 to PND 7 and exposed for 30 minutes to cold (4oC) or hot (37o C) stress on alternating days. Control group included littermates (LMC) who stayed with the dam and age-matched (AMC) litters raised without any intervention. This MS paradigm resulted in altered CORT release, anxiety and social behavior, as well as changes in brain structure and plasticity. Altered levels of mature BDNF (mBDNF) in the cortex and hippocampus of stressed (STR) mice were seen as well. This thesis, examines if BDNF level changes can be seen in adolescence, a typical age of onset for depression; altered social behavior in adolescence is seen in our model. We hypothesized that mBDNF levels would be lower and precursor BDNF (pro-BDNF) would be higher in cortex and hippocampus of stressed adolescent mice, at postnatal day 30, compared to the control group. I have examined the cortex and hippocampus of STR (N=20), LMC (N=10), and AMC (N=18) male and female mice who were sacrificed at PND 30. Brains were extracted and dissected on ice and stored at -70o C until they were processed for Western blot analysis of mBDNF and pro-BDNF. Multiple technical difficulties were encountered throughout this study hampering data generation and results returned inconclusive. I will discuss this process of trouble shooting my experiments and lessons learned from this study.