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:

(Date:5/12/2016)... May 12, 2016 , a ... the overview results from the Q1 wave of its ... wave was consumers, receptivity to a program where they ... a health insurance company. "We were surprised ... says Michael LaColla , CEO of Troubadour Research, ...
(Date:5/3/2016)... 3, 2016  Neurotechnology, a provider of high-precision ... Automated Biometric Identification System (ABIS) , a complete ... MegaMatcher ABIS can process multiple complex biometric transactions ... of fingerprint, face or iris biometrics. It leverages ... and MegaMatcher Accelerator , which have been ...
(Date:4/28/2016)... 28, 2016 First quarter 2016:   ... compared with the first quarter of 2015 The gross ... M (loss: 18.8) and the operating margin was 40% (-13) ... Cash flow from operations was SEK 249.9 M (21.2) , ... is unchanged, SEK 7,000-8,500 M. The operating margin for ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016 A person commits a crime, and the ... track the criminal down. An outbreak of foodborne ... Administration (FDA) uses DNA evidence to track down the bacteria ... far-fetched? It,s not. The FDA has increasingly used a complex, ... foodborne illnesses. Put as simply as possible, whole genome sequencing ...
(Date:6/23/2016)...  The Prostate Cancer Foundation (PCF) is pleased to announce 24 ... for prostate cancer. Members of the Class of 2016 were selected from a ... Read More About the Class of 2016 PCF Young Investigators ... ... ...
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, the Industry Network ... Supplyframe Design Lab . Located in Pasadena, Calif., the Design Lab’s mission is ... projects are designed, built and brought to market. , The Design Lab is ...
(Date:6/23/2016)... , June 23, 2016 Apellis ... Phase 1 clinical trials of its complement C3 ... single and multiple ascending dose studies designed to ... (PD) of subcutaneous injection in healthy adult volunteers. ... (SC) either as a single dose (ranging from ...
Breaking Biology Technology: