Emerging research tracks the physical effects from stress from neurosteroids acting on specific receptors in the brain.

Neuroscience researchers from Tufts University report they have been able to block this response in mice. Investigators believe these critical receptors may be drug therapy targets for control of the stress-response pathway.

This finding may lead to a variety of new approaches to manage a wide range of neurological disorders involving stress.

“We have identified a novel mechanism regulating the body’s response to stress by determining that neurosteroids are required to mount the physiological response to stress,” said author Jamie Maguire, Ph.D. “Moreover, we were able to completely block the physiological response to stress as well as prevent stress-induced anxiety.”

The association between stress and cortisol has been well-established. Scientists believe a stress-control pathway, more technically known as the Hypothalamus-Pituitary-Adrenal (HPA) axis, determines the levels of cortisol and other stress hormones in the human body.

An imbalance of hormones is implicated in the types of emotional and psychological stress that can lead to major depression.

Disorders of the stress-control pathway are also associated with obesity, premenstrual syndrome, postpartum depression, Cushing’s syndrome (hypercortisolism) and diseases including epilepsy and osteoporosis.

Using the brain tissues of adult mice, the research team identified mechanisms controlling the activity of Corticotrophin Releasing Hormone (CRH) neurons involved in the control of the stress pathway.

By monitoring the activity of CRH neurons following stress and measuring levels of corticosterone in the blood, they found that the production of stress hormones required the action of neurosteroids on specific receptors on CRH neurons. Investigators also discovered that stress causes a neurosteroid-induced increase in blood corticosterone levels.

The researchers also found that blocking the synthesis of neurosteroids is sufficient to block the stress-induced elevations in corticosterone and prevent stress-induced, anxiety-like behavior in mice.

“We have found a definite role of neurosteroids on the receptors regulating CRH nerve cells and the stress response. The data suggest that these receptors may be novel targets for control of the stress-control pathway.

“Our next work will focus on modulating these receptors to treat disorders associated with stress, including epilepsy and depression-like behaviors,” said Maguire.

Source: Tufts University