MIT finds cure for fear

Submitted by Vidura Panditaratne on Sun, 2007-07-15 19:37.


MIT biochemists have identified a molecular mechanism behind fear, and successfully cured it in mice, according to an article in the journal Nature Neuroscience.

Researchers from MIT’s Picower Institute for Learning and Memory
hope that their work could lead to the first drug to treat the millions
of adults who suffer each year from persistent, debilitating fears –
including hundreds of soldiers returning from conflict in Iraq and

Inhibiting a kinase, an enzyme that change proteins, called Cdk5
facilitates the extinction of fear learned in a particular context,
Li-Huei Tsai, Picower Professor of Neuroscience in the Department of
Brain and Cognitive Sciences, and colleagues showed.

Conversely, the learned fear persisted when the kinase’s activity
was increased in the hippocampus, the brain’s center for storing
memories, the scientists found.

Cdk5, paired with the protein p35, helps new brain cells, or
neurons, form and migrate to their correct positions during early brain
development, and the MIT researchers looked at how Cdk5 affects the
ability to form and eliminate fear-related memories.

“Remarkably, inhibiting Cdk5 facilitated extinction of learned fear
in mice,” Tsai said. “This data points to a promising therapeutic
avenue to treat emotional disorders and raises hope for patients
suffering from post-traumatic stress disorder or phobia.”

Emotional disorders such as post-traumatic stress and panic attacks
stem from the inability of the brain to stop experiencing the fear
associated with a specific incident or series of incidents.

For some people, upsetting memories of traumatic events do not go
away on their own, or may even get worse over time, severely affecting
their lives.

A study conducted by the Army in 2004 found that one in eight
soldiers returning from Iraq reported symptoms of post-traumatic stress
disorder (PTSD).

According to the National Center for PTSD in the United States,
around eight percent of the population will have PTSD symptoms at some
point in their lives. Some 5.2 million adults have PTSD during a given
year, the center reports.

In the current research, genetically engineered mice received mild
foot shocks in a certain environment and were re-exposed to the same
environment without the foot shock.

The team found that mice with increased levels of Cdk5 activity had
more trouble letting go of the memory of the foot shock and continued
to freeze in fear.

The reverse was also true: in mice whose Cdk5 activity was
inhibited, the bad memory of the shocks disappeared when the mice
learned that they no longer needed to fear the environment where the
foot shocks had once occurred.

“In our study, we employ mice to show that extinction of learned
fear depends on counteracting components of a molecular pathway
involving the protein kinase Cdk5,” Tsai concluded. “We found that Cdk5
activity prevents extinction, at least in part by negatively affecting
the activity of another key kinase.”

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