Navigation Links
Depression model leaves mice with molecular scar

In addition to triggering a depression-like social withdrawal syndrome, repeated defeat by dominant animals leaves a mouse with an enduring "molecular scar" in its brain that could help to explain why depression is so difficult to cure, suggest researchers funded by the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH).

In mice exposed to this animal model of depression, silencer molecules turned off a gene for a key protein in the brain's hippocampus. By activating a compensatory mechanism, an antidepressant temporarily restored the animals' sociability and the protein's expression, but it failed to remove the silencers. A true cure for depression would likely have to target this persistent stress-induced scar, say the researchers, led by Eric Nestler, M.D., The University of Texas Southwestern Medical Center, who report on their findings online in Nature Neuroscience during the week of February 26, 2005.

"Our study provides insight into how chronic stress triggers changes in the brain that are much more long-lived than the effects of existing antidepressants," explained Nestler.

Mice exposed to aggression by a different dominant mouse daily for 10 days became socially defeated; they vigorously avoided other mice, even weeks later. Expression of a representative gene in the hippocampus, a memory hub implicated in depression, plummeted three-fold and remained suppressed for weeks. However, chronic treatment with an antidepressant (the tricyclic imipramine) restored expression of the gene for brain derived neurotrophic factor (BDNF) to normal levels and reversed the social withdrawal behavior. BDNF in the hippocampus has been linked to memory, learning and depression, but Nestler said social defeat stress probably similarly affects other genes there as well.

The researchers pinpointed how social defeat changes the BDNF gene's internal machinery. They traced the gene expression changes to long-lasting mo difications in histones, proteins that regulate the turning on-and-off of genes via a process called methylation. Methyl groups, the silencer molecules, attach themselves to the histones, turning off the gene. Notably, imipramine was unable to remove these silencer molecules, suggesting that they remained a latent source of vulnerability to future depression-like responses to stress.

Imipramine reversed the suppressed BDNF gene expression by triggering a compensatory mechanism, acetylation, in which molecular activators attach themselves to the gene and overcome the silencer molecules. Imipramine turned off an enzyme (Hdac5) that degrades the activators, allowing them to accumulate.

"The molecular scar induced by chronic stress in the hippocampus, and perhaps elsewhere in the brain, can't be easily reversed," said Nestler. "To really cure depression, we probably need to find new treatments that can remove the silencer molecules."


'"/>

Source:NIH/National Institute of Mental Health


Related biology news :

1. Depression gene may weaken mood-regulating circuit
2. Scientists identify new model Of NK cell development
3. Genrate: a generative model that finds and scores new genes and exons in genomic microarray data
4. Molecular models advance the fight against malaria
5. NYU and MSKCC research provides model for understanding chemically induced cancer initiation
6. Genetic therapy reverses nervous system damage in animal model of inherited human disease
7. Disease progression model of pancreatic cancer developed by Penn researchers
8. A new way to share models of biological systems
9. Understanding biases in epidemic models important when making public health predictions
10. Climate model links higher temperatures to prehistoric extinction
11. Gene therapy advance treats hemophilia in mouse models
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/16/2017)... TEANECK, N.J. , May 16, 2017  Veratad ... leading provider of online age and identity verification solutions, ... the K(NO)W Identity Conference 2017, May 15 thru May ... Ronald Regan Building and International Trade Center. ... across the globe and in today,s quickly evolving digital ...
(Date:4/18/2017)... , April 18, 2017  Socionext Inc., a global expert in ... media edge server, the M820, which features the company,s hybrid codec ... provided by Tera Probe, Inc., will be showcased during the upcoming ... NAB show at the Las Vegas Convention ... Click ...
(Date:4/11/2017)... Apr. 11, 2017 Research and Markets has ... report to their offering. ... The global eye tracking market to grow at a CAGR of ... Eye Tracking Market 2017-2021, has been prepared based on an in-depth ... market landscape and its growth prospects over the coming years. The ...
Breaking Biology News(10 mins):
(Date:6/23/2017)... ... June 23, 2017 , ... Ken Hanson, a medical ... Physik Instrumente USA, have been selected as this year’s recipients of two top awards ... have been invited along with other honorees to accept their awards at a banquet ...
(Date:6/22/2017)... ... 21, 2017 , ... RMC Pharmaceutical Solutions, Inc. announces the ... to manage the new site. , Tim has 25 years of pharmaceutical experience, ... role as the Director of Manufacturing and Supplier Quality Assessment. This group ...
(Date:6/22/2017)... ... 22, 2017 , ... For the months of May and ... Spotlight series on “Cell Therapy Regulation” for its regenerative medicine followship. ... unique regulatory challenges of stem cell medical research. , Stem cell clinical trials ...
(Date:6/22/2017)... ... 22, 2017 , ... Charm Sciences, Inc. is pleased to announce that its ... be appropriate as a screening test at dairies and farms for raw commingled cow ... the Charm EZ Lite system. These systems are a combination incubator and reader in ...
Breaking Biology Technology: