Selective reduction of fear-related memories by targeting the epigenome

28 Aug 2012

Scared of heights? Spiders? Sharks, perhaps?

Scientists at the Queensland Brain Institute (QBI) at The University of Queensland (UQ) have discovered a novel mechanism which may eradicate fearful memories.

Neuroscientist Dr Timothy Bredy, has spent several years studying an inhibitory learning process known as fear extinction, which is the explicit preclinical model of exposure therapy for the treatment of fear-related anxiety disorders.

“Fear extinction is the gradual reduction in the fear response by repeated presentation of fear evoking cues in a non-threatening way that is thought to generate a new memory, which relies, in part, on destabilisation of the original fear-related memory trace,” he explains.

“By selectively modulating the processes that control the expression of genes associated with memory retrieval, we have seen a subsequent reduction of fear-related memories.”

Dr Bredy and his laboratory also worked not only to determine how fear is extinguished, but also to ensure it does not return.

“Through a series of experiments exploring this process, we have been able to pinpoint a molecular mechanism responsible for eliminating existing fears and preventing their renewal.”

The research group focuses on the so-called “epigenome”, which represents a layer of control over how genes function without changing the DNA sequence. They also study how its modulation can result in changes in gene expression and long-term memory.

“In recent years, there have been major advances in our understanding of the interface between genes and the environment and how this relates to fear-related learning and memory. The rapidly emerging field of cognitive neuroepigenetics is a reflection of this effort”.

“By examining the epigenetic machinery and gene expression associated with the retrieval and subsequent extinction of fear-related memory, w have learned that there are specific epigenetic mechanisms that regulate the formation of memory for fear extinction”, said postdoctoral fellow, Dr Wei Wei, a lead author on the study.

Dr Wei says this work will aid the development of better treatments for people afflicted with phobias and post-traumatic stress disorder.

“Now that we have gained a better understanding of how fear-related memories can be destabilised in order to promote the process of fear extinction, we have a target for the treatment of fear-related anxiety disorders and can begin developing targeted therapeutic interventions.”

This means, rather than simply using behavioural therapy for fear-related anxiety disorders, patients may one day be treated using a combination of exposure therapy and a highly specific pharmacological adjunct, which targets epigenetic processes.

These findings were recently published in the prestigious Journal of Neuroscience.