Growth of dendrites and spines in the BLA caused either by stress or BDNF overexpression to enhanced anxiety-like behavior. This is relevant in light of our results showing that the same time points when stress triggers higher anxiety is also when BDNF is elevated in the BLA. For instance, both anxiety and BDNF are increased 1 and 21 days after CIS. Interestingly, BDNF mRNA has been shown to be elevated transiently in the BLA 2 hours after cued fear conditioning and such a temporally restricted elevation of BDNF signaling is believed to be a key step in the formation of a cuespecific fear. In contrast, a more sustained up-regulation of BDNF in the BLA may underlie the pathological increase in fear and anxiety observed following stress.
Hippocampal memory and synaptic plasticity also depend on BDNF, and reduced levels of BDNF following chronic stress is consistent with a large body of evidence showing impairment of hippocampal function and loss of hippocampal volume caused by stress. Further as hippocampal BDNF is critically involved in resilience to stress, any reduction can enhance vulnerability to stress. Therefore, the opposite effects on BDNF in the amygdala and hippocampus may provide a molecular basis for the contrasting behavioral effects of stress on memories encoded by these two brain areas. Moreover, these two brain areas differ not only in their response to stress, but also in how they regulate the stress response. While the hippocampus exerts a negative feedback regulation of the stress response via the HPA axis, the amygdala has the opposite effect. Therefore, the differential effects on BDNF in these two brain regions following stress could lead to an imbalance in HPA axis function through a gradual loss of hippocampal inhibitory control as well as a gain in excitatory control exerted by the amygdala. The regional differences in the pattern of BDNF expression triggered by stress also pose a significant challenge for pharmacological interventions aimed at countering the effects of stress on the amygdala and hippocampus.
Therefore, elucidation of the mechanisms behind the differential effects of stress on BDNF in the hippocampus and amygdala is likely to provide useful insights into novel therapeutic interventions against stress-related psychiatric disorders that are characterized by impaired cognitive function and abnormally high fear and anxiety. Hypertrophic cardiomyopathy is the most common inherited cardiac disease and is the leading cause of sudden cardiac death in young individuals. It is caused by genetic mutations encoding sarcomere proteins and the clinical diagnosis is characterized by unexplained left ventricular hypertrophy. However, HCM phenotypic expression is extremely variable and some patients may show only mild LVH or normal left ventricular thickness. Genetic testing for pathogenic mutations allows for a certain diagnosis and identification of HCM WY 14643 mutation carriers before, and independent of, the development of LVH. However, genetic testing, due to the large HCM genetic heterogeneity, is complex, time-consuming and expensive. Therefore, novel and sensitive diagnostic tests are needed for cascade family screening in order to identify HCM patients at an early stage. Initial studies using tissue Doppler imaging showed that mutation carriers without an overt HCM phenotype may have subtle myocardial diastolic dysfunction, as an early marker of the disease.