Brain Derived Neurotrophic Factor (BDNF) mRNA Expression Levels in Mice Exposed to Learned Helplessness

Brain Derived Neurotrophic Factor (BDNF) is associated with changes in cellular structure that occur during the development of the nervous system, and in the adult brain contributes to neural plasticity. BDNF is found in high concentrations in both the frontal cortex and hippocampus where it has been proposed to play a role in cognition and learning respectively. Low serum BDNF levels can be measured in patients with major depressive disorder, and there is a correlation between decreased BDNF levels and the severity of depression. At this time, research is attempting to solve the question of whether depression results secondary to diminished BDNF levels, or a reduction in BDNF levels occurs as a result of individuals becoming depressed. Learned Helplessness (LH) is utilized as a model for depression and this is confirmed due to the fact that LH is blocked by antidepressant medications. An advantage of using LH to induce depressive behavior is the fact that the onset of depression in an animal is at a defined time point. The model of Learned Helplessness allows for analysis of depressed patients via LH mice which at this current time is the most accurate model for depression. In this study, our results were consistent with the hypothesis that since BDNF levels are significantly reduced in the medial frontal cortices and hippocampus of depressed patients, as well as in several studies looking at depression in rodents, then BDNF mRNA levels would also be reduced in the brain tissue of LH mice compared to controls after induction of Learned Helplessness. We also predicted that the decrease in the amount of BDNF transcripts would be greater in the medial frontal cortical region (MFC) compared with hippocampal tissue, since deficits in this region have been identified in depressed patients. This was also found to be true in this experiment. The hypothesis was tested by measuring the mRNA message for the five BDNF transcript variants in both the hippocampus and the medial frontal cortex in mice that had experienced inescapable unpredicted foot shocks during learned helplessness training. This data was compared to control mice that did not experience the Learned Helplessness training. Differences in BDNF mRNA levels were then determined thereafter. Levels of mRNA BDNF in the HPC and MFC of both experimental LH and control animals were quantified using RT-PCR technique