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:2/13/2017)... Former 9/11 Commission border counsel and Special ... Kephart of Identity Strategy Partners, LLP, today releases ... "Executive Order: Protecting the Nation From Foreign Terrorist Entry ... "As President Trump,s ,Travel Ban, Executive Order gains more ... the travel ban, it is important that our national ...
(Date:2/8/2017)... 2017 About Voice Recognition Biometrics Voice recognition ... against a stored voiceprint template. Acoustic features of ... tone are compared to distinguish between individual voices. ... most PCs already have a microphone and can ... biometrics are most likely to be deployed in ...
(Date:2/8/2017)... 7, 2017 The biometrics market has ... confluence of organizations, desires to better authenticate or ... (password and challenge questions), biometrics is quickly working ... The market is driven by use cases, though ... and enterprise uses cases, with consumer-facing use cases ...
Breaking Biology News(10 mins):
(Date:2/23/2017)... , Feb. 23, 2017  Capricor Therapeutics, Inc. (NASDAQ: ... other medical conditions, today announced that Linda Marbán, Ph.D, president ... upcoming investor conferences: Cowen and Company ... 10:00 am ET Boston, MA ... at 9:00 am PT (12:00 pm ET) Dana ...
(Date:2/23/2017)... USA, and CARDIFF, UK (PRWEB) , ... February ... ... international society for optics and photonics , have been named Fellows of the ... significant scientific and technical contributions in the multidisciplinary fields of optics, photonics, and ...
(Date:2/22/2017)... ... ... Park Systems , a leader in Atomic Force Microscopy (AFM) since ... attendees and Park customers on Feb. 27, 2017 from 12-2pm at Morton’s The Steakhouse ... The luncheon will feature a talk on Automated AFM for Small-Scale and Large-Scale Surface ...
(Date:2/22/2017)... Fort Washington, PA (PRWEB) , ... ... ... The Omnia-Prova Education Collaborative (TOPEC), the leading medical education provider of ... Accreditation with Commendation by the Accreditation Council for Continuing Medical Education (ACCME). ...
Breaking Biology Technology: