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)... -- Veratad Technologies, LLC ( www.veratad.com ), an innovative and ... solutions, announced today they will participate as a sponsor ... May 17, 2017, in Washington D.C.,s ... Identity impacts the lives of billions of ... digital world, defining identity is critical to nearly every ...
(Date:4/19/2017)... 19, 2017 The global military ... is marked by the presence of several large global ... by five major players - 3M Cogent, NEC Corporation, ... for nearly 61% of the global military biometric market ... the global military biometrics market boast global presence, which ...
(Date:4/13/2017)... April 13, 2017 According to a new market ... Identity Analytics, Identity Administration, and Authorization), Service, Authentication Type, Deployment Mode, Vertical, ... Market is expected to grow from USD 14.30 Billion in 2017 to ... of 17.3%. ... MarketsandMarkets Logo ...
Breaking Biology News(10 mins):
(Date:6/22/2017)... Colorado (PRWEB) , ... June 21, 2017 , ... ... RTP regional office in North Carolina, and engages Timothy Reinhardt to manage the ... of quality leadership at Pfizer Inc, with his most recent role as the ...
(Date:6/22/2017)... ... June 22, 2017 , ... AESKU.GROUP, ... DST Diagnostische Systeme & Technologien GmbH, thereby expanding its product portfolio to include ... hay fever, urticaria, asthma, atopic eczema or a food allergy. Allergies are escalating ...
(Date:6/22/2017)... ... June 22, 2017 , ... For the months of May ... Spotlight series on “Cell Therapy Regulation” for its regenerative medicine followship. ... the unique regulatory challenges of stem cell medical research. , Stem cell clinical ...
(Date:6/22/2017)... Yorba Linda, Ca (PRWEB) , ... June 22, 2017 , ... ... labs worldwide. It took 20 years until the first data on cross-contamination of human ... cell lines has been an increasing issue in cell culture labs and is associated ...
Breaking Biology Technology: