Navigation Links
Lack of protein FKBP51 in old mice improves resilience to depressive behavior
Date:9/16/2011

Tampa, FL (Sept. 15, 2011) -- Decreasing expression of a protein associated with susceptibility to depression made old mice resistant to depressive-like behavior while improving their hormonal response to stress, a study led by researchers at the University of South Florida found. The lack of this protein, FKBP51, did not adversely affect their memory, learning, or basic motor functions.

The study suggests that drug discovery efforts aimed at reducing levels of the protein FKBP51 may yield new antidepressant therapies. The findings appear online today (Sept. 15, 2011) in the journal PLoS ONE.

The multidisciplinary research team included scientists from Vanderbilt University Medical Center and the University of Texas at El Paso as well as the USF Health Byrd Alzheimer's Institute.

"About a third of patients are resistant to treatment with standard antidepressant medications, so we need to look for other potential therapeutic targets," said principal investigator Chad Dickey, PhD, assistant professor of molecular medicine at the USF Health Byrd Alzheimer's Institute.

"We've shown that, because FKBP51 appears to act on the genetic liability to abnormal mood and anxiety states, it may offer a much needed treatment tool for secondary prevention of depression recurrence and relapse."

Dickey and his colleagues were using a mouse model with the FKBP5 gene deleted to help study the potential role of the protein it produces, FKBP51, in the progression of Alzheimer's disease. The protein increases with old age, and a reduction of FKBP51 levels has been shown to decrease the burden of tau, a hallmark protein associated with Alzheimer's disease.

FKBP51, a protein encoded by the FKBP5 gene, is highly expressed in the hypothalamus-pituitary-adrenal (HPA) axis, a major part of the brain's circuitry that controls neuroendocrine system responses to stress. Human genetic studies over the last decade have indicated that slight variations in the FKBP5 gene are associated with increased susceptibility to psychiatric disorders, including depression, post-traumatic stress disorder and anxiety.

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
abaier@health.usf.edu
813-974-3303
University of South Florida (USF Health)
Source:Eurekalert

Related biology news :

1. ORNL invention unravels mystery of protein folding
2. Protein found in heart may be target for colon cancer therapies
3. USC scientists identify key protein linked to acute liver failure
4. Scripps Research scientists pinpoint shape-shifting mechanism critical to protein signaling
5. Scientists find new drug candidates for set of protein-folding diseases
6. Foods rich in protein, dairy products help dieters preserve muscle and lose belly fat: study
7. Research offers new way to target shape-shifting proteins
8. Molecular chaperones traffic signaling proteins between cells in plant stem-cell maintenance pathway
9. Degrading proteins to divide cells
10. Protein in the urine spells kidney failure for African-Americans
11. Single protein, key to ebola virus infection, could aid in drug design
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/24/2017)... Janice Kephart , former 9/11 ... Partners, LLP (IdSP) , today issues the following ... March 6, 2017 Executive Order: Protecting the ... be instilled with greater confidence, enabling the reactivation ... applications are suspended by until at least July ...
(Date:4/18/2017)... Calif. , April 18, 2017  Socionext Inc., a global ... of a media edge server, the M820, which features the company,s ... recognition software provided by Tera Probe, Inc., will be showcased during ... at the NAB show at the Las Vegas ... ...
(Date:4/13/2017)... MONICA, Calif. , April 13, 2017 ... New York will feature emerging and evolving ... Summits. Both Innovation Summits will run alongside the expo ... of speaker sessions, panels and demonstrations focused on trending ... coast,s largest advanced design and manufacturing event will take ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... SANTA BARBARA, CALIFORNIA (PRWEB) , ... October 10, ... ... risk management, technological innovation and business process optimization firm for the life sciences ... the BoxWorks conference in San Francisco. , The presentation, “Automating GxP ...
(Date:10/9/2017)... ... 09, 2017 , ... The award-winning American Farmer television series will feature 3 ... airs Tuesdays at 8:30aET on RFD-TV. , With global population estimates nearing ten ... to continue to feed a growing nation. At the same time, many of our ...
(Date:10/9/2017)... (PRWEB) , ... October 09, ... ... published on October 5, 2017, in the medical journal, Epilepsia, Brain Sentinel’s ... the gold standard, video EEG, in detecting generalized tonic-clonic seizures (GTCS) using ...
(Date:10/7/2017)... , Oct. 6, 2017  The 2017 Nobel ... three scientists, Jacques Dubochet, Joachim Frank ... in cryo-electron microscopy (cryo-EM) have helped ... the structural biology community. The winners worked with ... now routinely produce highly resolved, three-dimensional images of ...
Breaking Biology Technology: