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September 11, 2007

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How fear memories take hold

July 16, 2007
Courtesy MIT
and World Science staff

Re­search­ers have un­cov­ered a mo­lec­u­lar mech­an­ism that they say gov­erns the forma­t­ion of fears stem­ming from trau­mat­ic events. The work could lead to the first drug to treat the mil­lions of adults who suf­fer each year from per­sist­ent, de­bil­i­tat­ing fears, they add, in­clud­ing sol­diers re­turn­ing from Iraq and Af­ghan­i­stan.

The find­ings ap­pear in the July 15 ad­vance on­line pub­lica­t­ion of the re­search jour­nal Na­ture Neu­ro­sci­ence.

A 2004 study found that one in eight sol­diers re­turn­ing from Iraq re­ported symp­toms of post-trau­mat­ic stress dis­or­der, an anx­i­e­ty con­di­tion as­so­ci­at­ed with trau­mat­ic events. About eight per­cent of the popula­t­ion will suf­fer from it at some point, ac­cord­ing to the U.S. Na­tional Cen­ter for Post-Traumatic Stress Dis­or­der.

In the new stu­dy, Neu­ro­sci­ent­ist Li-Huei Tsai of the Mas­sachus­sets In­sti­tute of Tech­nol­o­gy in Cam­bridge, Mass. and col­leagues found that in­hibit­ing the ac­ti­vity of a mol­e­cule in the brain called Cdk5 helps to elim­i­nate fears learn­ed in a par­tic­u­lar con­text. Con­verse­ly, the learn­ed fear per­sisted when the ac­ti­vity of the mol­e­cule, known as a ki­nase, was in­creased in the hip­po­cam­pus, the brain’s cen­ter for stor­ing mem­o­ries. 

Cdk5, a type of en­zyme, along with a pro­tein mol­e­cule p35, helps new brain cells, or neu­rons, form and mi­grate to their cor­rect po­si­tions dur­ing early brain de­vel­op­ment, ac­cord­ing to Tsai and col­leagues.

“Re­mark­ably, in­hibit­ing Cdk5 fa­cil­i­tat­e ex­tinc­tion of learn­ed fear in mice. 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,” Tsai said.

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Researchers have uncovered a molecular mechanism that they say governs the formation of fears stemming from traumatic events. The work could lead to the first drug to treat the millions of adults who suffer each year from persistent, debilitating fears, they add, including hundreds of soldiers returning from conflict in Iraq and Afghanistan. The findings appear in the July 15 advance online publication of the research journal Nature Neuroscience. A 2004 study found that one in eight soldiers returning from Iraq reported symptoms of post-traumatic stress disorder, an anxiety condition associated with traumatic events. About eight percent of the population will suffer from it at some point, according to the U.S. National Center for Post-Traumatic Stress Disorder. In the new study, Neuroscientist Li-Huei Tsai of the Massachussets Institute of Technology in Cambridge, Mass. and colleagues found that inhibiting the activity of a molecule in the brain called Cdk5 helps to eliminate fears learned in a particular context. Conversely, the learned fear persisted when the activity of the molecule, known as a kinase, was increased in the hippocampus, the brain’s center for storing memories. Cdk5, a type of enzyme, along with a protein molecule p35, helps new brain cells, or neurons, form and migrate to their correct positions during early brain development, according to Tsai and colleagues. “Remarkably, inhibiting Cdk5 facilitated extinction of learned fear in mice. 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,” Tsai said.