The researchers decided to examine for the first time whether old mice without the FKBP5 gene (and its protein by-product) were more resistant to depression using behavioral tests that routinely evaluate antidepressant effectiveness. They exposed two groups of old mice (17 to 20 months) to activities designed to induce depressive/stressed behavior. One group was FKBP5 deficient, while the other (littermates) was not.
"We wondered if the FKBP5-deficient mice would demonstrate more resilience, or greater antidepressant behavior, in response to the tests," said lead author John O'Leary, a PhD student in neuroscience at the USF Health Byrd Alzheimer's Institute.
They did, and without any apparent adverse consequences. The FKBP5-deficient mice performed as well as their littermates with the FKBP5 gene intact on tasks designed to test memory, learning and basic motor functions.
In an experiment coinciding with the observed effects on depression, the researchers discovered that corticosterone levels rose as expected in both the FKBP5-deficient mice and their non-deficient counterparts following a stressful activity. However, the amount of corticosterone circulating in the blood of the FKBP5-deficient mice was still lower than that measured in the non-FKBP5 mice. Corticosterone (known as cortisol in humans) is a steroid hormone released in response to stress and its levels are higher than normal in depressed patients.
The researchers suggest that the lack of the protein FKBP51 leads to a decrease in HPA-axis activities, including a weakening of stress hormones, which may improve resilience to depression.
|Contact: Anne DeLotto Baier|
University of South Florida (USF Health)