Investigators from the University of Pennsylvania Perelman School of Medicine say that a single molecule, the cellular protein HDAC6, may be used as a target for new therapies meant to prevent the development of associated disorders in people suffering from stress.
This condition is a known risk factor for depression and post-traumatic stress disorder (PTSD), both of which are debilitating conditions that significantly reduce sufferers' quality of life. By targeting HDAC6, it may be possible to increase the body's ability to withstand the negative effects of stress.
Researchers describe this molecule as a gatekeeper of steroid biology in the human brain. Its main mechanism of action is through mediating the effect of glucocorticoids on mood and emotions.
Glucocorticoids are a family of chemicals that are secreted in the body whenever we are exposed to stress. They are not harmful in small doses, but can have adverse effects when their concentrations spike. Studies have linked them to an increased predisposition to developing stress-related conditions.
These substances act on receptors in the nucleus of emotion–regulating neurons. They can therefore exert direct effects on mood, which is why they are so well equipped to trigger depression. The chemicals can also affect the neural receptors for the neurotransmitter serotonin.
Researchers have been trying to find a way of mediating the effects of glucocorticoids on the brain for quite some time now. The UPPSM group believed that HSDAC6 is capable of producing these effects.
Assistant professor of psychiatry Olivier Berton, PhD, is the lead author of a new paper describing the findings, which is published in a recent issue of the esteemed medical Journal of Neuroscience.
He explains that this cellular protein contains a large number of serotonin pathways, which enables it to mediate the interactions between glucocorticoid receptors and hormones in serotonin circuits.
The investigation also suggests that HDAC6 may be used as a possible stress vulnerability biomarker. A simple test could be devised to measure levels of this protein in patients' bodies. This may help doctors figure out who is at the greatest risk of becoming depressed.
In addition, the work may allow progress in investigating the causes of PTSD, as well as potential early-detection tests. The US Army is especially interested in this line of study, given the high number of soldiers that develop the mental condition, Science Blog