Stressed-out mice reveal role of epigenetics in behavior

December 11, 2008

Research conducted by a team in Switzerland suggests that a family of genes involved in regulating the expression of other genes in the brain is responsible for helping us deal with external inputs such as stress. Their results, appearing in the December 11 advance online version of the journal Neuron, may also give a clue to why some people are more susceptible to anxiety or depression than others.

The researchers from EPFL and the National Competence Center "Frontiers in Genetics" studied the role of a family of genes known as KRAB-ZFP, which acts like a group of genetic censors, selectively silencing the expression of other genes. These repressors make up about 2% of our genetic material, but little is known about how this "epigenetic" silencing process works, what the long-term consequences are, and even which genes are targeted. (Epigenetics refers to a change in gene expression that is caused by something other than a change in the underlying DNA sequence.)

The researchers bred a strain of mice that lacked in the hippocampus, a part of the forebrain involved in short-term memory and inhibition, a key cofactor used by the KRAB family. The genetically altered mice appeared completely normal until they were placed in a stressful situation. Then they became extremely anxious. Although the normal mice quickly adapted, the altered mice never managed to overcome their stress, and remained anxious and unable to complete simple cognitive tasks. The disruption of the KRAB-mediated regulatory process thus altered the mice's normal behavioral response to stress.

"The KRAB regulators appeared fairly recently on an evolutionary scale," notes EPFL professor Didier Trono, lead author on the study, " and it's very likely that there is a fair degree of polymorphism between individuals. We postulate that variability in these genes is one factor that may participate in predisposing people to anxiety syndromes or depression. "

Because epigenetic alterations are often long-lasting and sometimes permanent, one could also interpret them as a way in which an individual's personal history can have a lasting impact on his or her genetic expression. "It's a way for a cell to have a sort of memory," explains Trono.

This work opens promising leads for further exploration, because evidence of epigenetic modification has been observed in animal models of depression, addiction, schizophrenia and neuro-developmental disorders. Some psychoactive drugs like cocaine or anti-psychotics also cause changes in some of the co-factors involved in this genetic regulatory system. With an understanding of the molecular mechanisms involved in epigenetic modulation, it might be possible to develop targeted therapies for those individuals in whom it malfunctions.

Source: Ecole Polytechnique Fédérale de Lausanne

Explore further: Immune cells turn back time to achieve memory

Related Stories

Immune cells turn back time to achieve memory

December 13, 2017
Memory T cells earn their name by embodying the memory of the immune system - they help the body remember what infections or vaccines someone has been exposed to. But to become memory T cells, the cells go backwards in time, ...

Modulating immune responses

December 13, 2017
The protein Roquin plays a key role in the regulation of immune reactions. LMU researchers have now uncovered details of the mechanism by which it controls the function of regulatory T cells in the adaptive arm of the immune ...

Role of transcriptional co-factor hints at possible inflammatory bowel disease treatment

December 12, 2017
Inflammatory bowel disease (IBD), including the two conditions ulcerative colitis and Crohn's disease, results in long-term inflammation of the gut and is associated with dysregulation of the immune system. However, it is ...

Cancer-causing mutation suppresses immune system around tumours

December 12, 2017
Mutations in 'Ras' genes, which drive 25% of human cancers by causing tumour cells to grow, multiply and spread, can also protect cancer cells from the immune system, finds a new study from the Francis Crick Institute and ...

Newly published research provides new insight into how diabetes leads to retinopathy

December 7, 2017
An international team of scientists led by Professor Ingrid Fleming of Goethe University, Frankfurt, Germany, and including Professor Bruce Hammock of the University of California, Davis, provides new insight into the mechanism ...

Researchers discover spinal cord neurons that inhibit distracting input to focus on task at hand

December 8, 2017
We think of our brain as masterminding all of our actions, but a surprising amount of information related to movement gets processed by our spinal cord.

Recommended for you

Drug found that induces apoptosis in myofibroblasts reducing fibrosis in scleroderma

December 15, 2017
(Medical Xpress)—An international team of researchers has found that the drug navitoclax can induce apoptosis (self-destruction) in myofibroblasts in mice, reducing the spread of fibrosis in scleroderma. In their paper ...

How defeating THOR could bring a hammer down on cancer

December 14, 2017
It turns out Thor, the Norse god of thunder and the Marvel superhero, has special powers when it comes to cancer too.

Researchers track muscle stem cell dynamics in response to injury and aging

December 14, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) describes the biology behind why muscle stem cells respond differently to aging or injury. The findings, published in Cell Stem Cell, ...

'Human chronobiome' study informs timing of drug delivery, precision medicine approaches

December 13, 2017
Symptoms and efficacy of medications—and indeed, many aspects of the human body itself—vary by time of day. Physicians tell patients to take their statins at bedtime because the related liver enzymes are more active during ...

Study confirms link between the number of older brothers and increased odds of being homosexual

December 12, 2017
Groundbreaking research led by a team from Brock University has further confirmed that sexual orientation for men is likely determined in the womb.

Potassium is critical to circadian rhythms in human red blood cells

December 12, 2017
An innovative new study from the University of Surrey and Cambridge's MRC Laboratory of Molecular Biology, published in the prestigious journal Nature Communications, has uncovered the secrets of the circadian rhythms in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.