Gene Dog Blog

Depression is one of the most common and most poorly understood health problems. About 10% of adults in the U.S. suffer from depression. The etiology of depression is largely unknown, however, environmental factors, such as chronic stress, can increase the chances that an individual will develop depressive symptoms. While most people encounter stressful events at some points in their lives, not all of these people suffer from depression. Until recently, the molecular mechanisms underlying the variability in susceptibility to depression remained unknown. A recent study published in Neuron discusses the role of epigenetics of neuronal cells in the etiology and pathophysiology of depression.

The authors of the study modeled depression on mice to investigate susceptibility to depression symptoms such as anhedonia, anxiety and loss of interest. Mice were exposed to mild stress over a period of six weeks and were then tested for symptoms of depression against a control group that was not exposed to stress using standard tests for mouse depression models. Notable differences were observed within the experimental, stressed group. Only some of the stressed mice exhibited symptoms of depression, while others showed little or no change in behavior. The depressive symptoms were reversed by the administration of a trycyclic antidepressant.

To examine the differences between the stress-susceptible and stress-resilient mice the authors of the study looked at mRNA expression of neurotrophic factors in different regions of the brain. The most notable differences were observed in the expression of glial cell-derived neurotrophic factor (Gdnf) in the striatum. Chronic stress was shown to reduce Gdnf expression in the stress-susceptible mice, but not in the stress-resilient mice. This difference was traced to the epigenetic status of the Gdnf promoter. In stress-susceptible mice the promoter of Gdnf was shown to be bound by significantly fewer acetylated histones. The authors of the study show that the main difference between these two groups of mice is the level of expression of certain histone deacetylases. The susceptibility to depression exhibited by some of the mice can be explained by an increase in histone deacetylase expression in reaction to chronic stress. The other mice did not exhibit such increase and, therefore, did not develop depressive symptoms.

This study is a major step toward elucidating the molecular basis for variability in depression susceptibility. The causes of epigenetic differences at the Gdnf promoter remain unknown but can most likely be attributed to various environmental and genetic factors. The epigenetic basis of this variability also points to new pharmocological targets for antidepressants. While drugs currently used to treat depression fall into the categories of tricyclics and seratonin reuptake inhibitors, histone deacetylase inhibitors could also prove to be effective.

By-line:
This guest post is contributed by Barbara Jolie, who writes for online classes. She welcomes your comments at her email Id: barbara.jolie876@gmail.com.

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