(PhysOrg.com) -- Researchers working with mice have discovered that by removing a protein from the region of the brain responsible for recalling fear, they can permanently delete traumatic memories. Their report on a molecular means of erasing fear memories in rodents appears this week in Science Express.
PhysOrg.com報導——研究老鼠的研究人員已經發現，通過移除老鼠大腦負責回憶恐懼的腦區中的一種蛋白質，他們就能夠永久地刪除老鼠的創傷性記憶。他們的研究發表在本周《科學》雜誌（Science Express）的預印本上，研究報告了擦除齧齒動物恐懼記憶的分子學方法。
「When a traumatic event occurs, it creates a fearful memory that can last a lifetime and have a debilitating effect on a person"s life,」 says Richard L. Huganir, Ph.D., professor and director of neuroscience at the Johns Hopkins University School of Medicine and a Howard Hughes Medical Institute investigator. 「Our finding describing these molecular and cellular mechanisms involved in that process raises the possibility of manipulating those mechanisms with drugs to enhance behavioral therapy for such conditions as post-traumatic stress disorder.」
「當一個創傷性事件發生時，它會創造一種可怕的記憶，這種記憶能夠終身存在，並且對一個人的生活產生衰弱效應，」美國約翰·霍普金斯大學（Johns Hopkins University）醫學院神經科學系主任以及教授理察·胡加尼爾（Richard L. Huganir）博士說。胡加尼爾博士同時也是霍華德·休斯醫學研究所（Howard Hughes Medical Institute）的研究者。「我們這項描述了參與擦除記憶過程的分子與細胞機制的發現，為通過藥物操控那些機制來增強針對創傷後應急障礙（PTSD）的行為療法效果提供了可能性。」
Behavioral therapy built around 「extinction training」 in animal models has proven helpful in easing the depth of the emotional response to traumatic memories, but not in completely removing the memory itself, making relapse common.
建立在動物模型中的「消失訓練」之上的行為療法，已經證明對擦除創傷性記憶的深度情緒反應是有作用的，但是卻無法完全移除創傷性記憶本身，這使得病情復發變得很普遍。
Huganir and postdoctoral fellow Roger Clem focused on the nerve circuits in the amygdala, the part of the brain known to underly so-called fear conditioning in people and animals. Using sound to cue fear in mice, they observed that certain cells in the amygdala conducted more current after the mouse was exposed to a loud, sudden tone.
胡加尼爾和他的博士後羅傑·克連（Roger Clem）集中關注大腦中杏仁核（amygdala）的神經迴路，杏仁核是人類與動物大腦中負責所謂恐懼調節的腦區。通過聲音促發老鼠產生恐懼，他們觀察到在老鼠被暴露在突然增大的聲音環境中之後，杏仁核中的某些細胞發放了更多的電流。
In hopes of understanding the molecular underpinnings of fear memory formation, the team further examined the proteins in the nerve cells of the amygdala before and after exposure to the loud tone. They found temporary increases in the amount of particular proteins — the calcium-permeable AMPARs — within a few hours of fear conditioning that peaked at 24 hours and disappeared 48 hours later.
懷著能夠理解恐懼記憶形成過程的分子基礎的希望，這個研究小組進一步檢測了暴露在響亮聲音之前和之後，杏仁核神經迴路中的蛋白質。他們發現一種特定的蛋白質——能夠滲透鈣離子的AMPARs蛋白——在恐懼出現的幾個小時之內出現了暫時性的增加，這種蛋白質的增加在恐怖出現之後24小時達到頂峰，並在恐懼出現48個小時之後消失。
Because these particular proteins are uniquely unstable and can be removed from nerve cells, the scientists proposed that they might permanently remove fear by combining behavior therapy and protein removal and provide a window of opportunity for treatment. 「The idea was to remove these proteins and weaken the connections in the brain created by the trauma, thereby erasing the memory itself,」 says Huganir.
因為這些特定的蛋白質具有獨特的不穩定性，並且能夠從神經細胞中被移除，所以科學家提出他們可能能夠通過結合行為療法與蛋白質移除永久性地擦除恐懼，而且為治療創傷性障礙提供了機會之窗。「這一思想就是移除這些蛋白質，並且削弱大腦中由創傷造成的連接，從而擦除創傷記憶本身，」胡加尼爾說。
In further experiments, they found that removal of these proteins depends on the chemical modification of the GluA1 protein. Mice lacking this chemical modification of GluA1 recovered fear memories induced by loud tones, whereas littermates that still had normal GluA1 protein did not recover the same fear memories. Huganir suggests that drugs designed to control and enhance the removal of calcium-permeable AMPARs may be used to improve memory erasure.
在進一步的實驗中，他們發現移除這些蛋白質要依賴於GluA1蛋白質的化學改質（chemical modification）。缺乏這種GluA1化學改質的老鼠會重新出現由響亮的聲音造成的恐懼記憶，而同窩出生的老鼠中仍然擁有正常GluA1蛋白質的老鼠不會重新出現相同的恐懼記憶。胡加尼爾提出，設計出藥物控制並且提高鈣離子可滲透性AMPARs蛋白質的可移除性，可能能夠被用來提高創傷記憶的擦除。
「This may sound like science fiction, the ability to selectively erase memories,」 says Huganir. 「But this may one day be applicable for the treatment of debilitating fearful memories in people, such as post-traumatic stress syndrome associated with war, rape or other traumatic events.」
「這種能夠選擇性擦除記憶的能力，可能聽起來像科幻小說，」胡加尼爾說。「但是，這可能有朝一日能夠被應用到人類衰弱恐懼記憶的治療中，比如與戰爭相關的創傷後精神壓力綜合症，被強姦後的創傷性記憶或者其他創傷性事件。」
This study was funded by the National Institutes of Health and the Howard Hughes Medical Institute.
這項研究由美國國家衛生研究院（NIH）與霍華德·休斯醫學研究所共同提供資助。
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