How Fear Modifies Genes

Scientists have found a genetic modification associated with the control of the fear response.

AsianScientist (May 2, 2014) – An international team of researchers, including neuroscientists from The University of Queensland’s Queensland Brain Institute (QBI), may have found a way to silence the genes that feed fear.

QBI senior research fellow Dr. Timothy Bredy said the team had shed new light on the processes involved in loosening the grip of fear-related memories, particularly those implicated in conditions such as phobia and post-traumatic stress disorder.

He said that by understanding the fundamental relationship between the way in which DNA functions without a change in the underlying sequence (epigenetics), future targets for therapeutic intervention in fear-related anxiety disorders could be developed.

“This may be achieved through the selective enhancement of memory for fear extinction by targeting genes that are subject to the novel mode of epigenetic regulation we have discovered,” he said.

While DNA methylation is a well-known epigenetic modification, the impact of another form of modification known as 5-hydroxymethylcytosine (5-hmC) is less well understood. Bredy and his team found that mice which underwent fear extinction training showed a change in the 5-hmC distribution patterns in the brain, suggesting that 5-hmC modification of DNA is critical for controlling fear when the response is no longer required. This research was published in the Proceedings of the National Academy of Sciences of the United States of America.

Li Xiang, a PhD candidate and the study’s lead author, said fear extinction was a clear example of rapid behavioral adaptation, and that impairments in this process were critically involved in the development of fear-related anxiety disorders.

“What is most exciting is that we have revealed an epigenetic state that appears to be quite specific for fear extinction,” Li said.

Bredy said this was the first comprehensive analysis of how fear extinction was influenced by modifying DNA.

“It highlights the adaptive significance of experience-dependent changes in the chromatin landscape in the adult brain,” he said.

The article can be found at: Li et al. (2014) Neocortical Tet3-mediated Accumulation of 5-hydroxymethylcytosine Promotes Rapid Behavioral Adaptation.

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Source: University of Queensland; Photo: dryhead/Flickr/CC.

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