Important Link in the Stress Response Could Mean Better Treatment

A team at Tufts University appears to have found an important step in the body’s stress reaction, and blocking this step from occurring can significantly reduce the response. The finding may pave the way for improved treatments for depression and anxiety.

The stress cascade is governed by the brain’s hypothalamus, which communicates with the pituitary and adrenal glands, which in turn secrete stress hormones like cortisol. Disruptions in this pathway are also connected with problems like postpartum depression, obesity, Cushing's syndrome (hypercortisolism), premenstrual syndrome (PMS), epilepsy, and osteoporosis, according to the study’s press release.

The team reasoned that disrupting the synthesis of the neurosteroids should significantly reduce the stress response, by stopping it almost before it begins.

Using mice as their subjects, the researchers set out to fill in some of the blanks in the cascade of events that leads to the secretion of the stress hormone coriticosterone (the mouse equivalent to our cortisol). They used brain samples from mice, and tracked the activity of the brain cells that release corticotrophin-releasing hormone (CRH), which ultimately stimulates the secretion of stress hormones.

They discovered that specific “neurosteroids” are needed to bind to receptors on the CRH neurons to activate them, serving as an important early step in the stress response. The team reasoned that disrupting the synthesis of the neurosteroids should significantly reduce the stress response, by stopping it almost before it begins.

This is just what they found. When they blocked the neurosteroids’ synthesis in live mice, their coriticosterone levels were reduced after stressful situations, compared to normal mice. Additionally, if neurosteroid synthesis was halted, the mice did not show anxiety-like behaviors after they had been stressed.

One of the authors, Jamie Maguire, said that 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."

The study is published in The Journal of Neuroscience.