1SOME mice can easily remember where they hide food, but not those genetically engineered to develop Alzheimer’s disease.Like humans they become forgetful. By the time these mice are seven months old they are unable to remember, for example, which arm of a maze they have explored before. Two months later, their brains are riddled with amyloid beta,the protein 「plaques」 that also characterise the latter stage of the disease in humans.
老鼠能輕易記起它們把食物藏在哪兒，但通過基因工程而患有痴呆症的老鼠卻不能。它們和人類一樣健忘。這些老鼠七個月大的時候就記不住，比如去過迷宮的哪條路。2個月之後，大腦就充滿了β-澱粉樣蛋白，這些蛋白質斑點同樣是痴呆症病人晚期的特徵。
2Now researchers have managed to restore memories to mice with Alzheimer’s. This helps provide more evidence about how memories are lost during the early stages of the disease and may point to how, some time in the future, those memories might be brought back.
現在研究者成功恢復了痴呆症老鼠的記憶。這提供了痴呆症早期是如何丟失記憶的線索，以及在未來記憶怎樣被恢復的關鍵。
3Susumu Tonegawa and his colleagues at the Massachusetts Institute of Technology used a technique known as optogenetics,which activates clusters of neurons by shining light on them. As they report in Nature, the researchers prepared seven-month-old Alzheimer’s mice by injectinga harmless virus into the rodents』 dentate gyrus, a part of the hippocampus that helps to store fearful memories. The virus contains a gene for channel rhodopsin-2, a light-sensitive protein which forms pores in the cell membranes of neurons infected with the virus. These pores are closed in the dark, but open in response to blue light, flooding neurons with positively charged ions. The resulting pulse of current makes the neurons fire. During their experiments, the researchers were able to illuminate the infected neurons of the mice using optical fibres implanted in their brains.
麻省理工學院的利根川進和同事用一種「光遺傳學」的技術，用光照刺激神經元集群。正如他們在《自然》上發表的那樣，研究人員將一種無害病毒注射到預先準備的七個月大痴呆症老鼠的齧齒動物齒狀回區，這個區域是海馬體內幫助存儲害怕記憶的一部分。病毒含有光敏感通道的基因，產生的光敏感蛋白能在被病毒感染的神經元細胞膜上形成通道。這些通道在無光照時是關閉的，但對藍光起反應並打開，使神經元充滿正離子。產生的電流脈衝使神經元產生電流。在實驗中，研究人員能用光纖植入老鼠大腦來刺激感染的神經元。
4Using a standard lab test of memory, a mouse was placed in a box and given a small electrical shock to its feet.Normal mice remember this and freeze in fear if put back in the box the following day, but mice with Alzheimer’s scamper about unfazed. Yet when the researchers stimulated the dentate gyrus of these mice with blue light, they also froze, suggesting that they were now able to recall the original shock.
用一個標準的實驗室記憶測試，一隻老鼠被放在盒子裡面並對它的腳給予微小電擊。如果接下來幾天把它放進盒子裡，正常老鼠會記住並且由於害怕而呆住不動，痴呆症老鼠則不受影響活蹦亂跳。但當研究人員用藍光刺激這些痴呆症老鼠的海馬體時，它們一樣會呆住不動，這表明它們能記起最初的電擊感受。
5Holding on to a fearful memory in the long term, however, requires the brain to strengthen the nerve connections (synapses) that link memory of the box to experience of the shock. This process, known as long-term potentiation, goes awry in the brains of Alzheimer’s patients. Consistent with this idea, the Alzheimer’s mice did not freeze when placed in the box but only when their neurons were illuminated.
可是要長時間保持住害怕記憶，要求大腦加強神經聯繫（突觸）來連結盒子裡的電擊實驗的記憶。這個過程，叫做長時程增強，沒能在痴呆症老鼠大腦裡順利進行。和這想法一致的是，把痴呆症老鼠放在盒子裡，僅僅照射神經元，老鼠並沒有呆住不動。
6To help the Alzheimer’s mice consolidate and keep their memory of the electric shock, the team flashed their dentategyrus with blue light at 100 hertz, a frequency known to induce long-termpotentiation. After this the Alzheimer’s mice froze in the box for at least six consecutive days, suggesting they were able to remember the shock themselves.
為了幫助痴呆症老鼠鞏固和保持它們對電擊的記憶，團隊用100赫茲的藍光照射它們的齒狀回，這個頻率能誘導長時程增強。這之後老鼠連續六天呆在盒子裡不動，表明它們能記住電擊感受。
7Work by other groups has suggested that in its early stages, Alzheimer’s principally damages the brain’s ability to process and store memories. This new work, however, indicates that it is the brain’s ability to retrieve memories that is impaired. The distinction is far from an academic one. If memories are garbled before they are stored, they are lost for ever. But if Dr Tonegawa is right, then memories are correctly preserved in the brains of Alzheimer’s patients. That means it may be possible to rescue them—perhaps by adapting optogenetics for use in human sufferers.That remains a distant possibility for now.
其他團隊的工作早就表明在早期階段，痴呆症主要破壞大腦加工和存儲記憶的能力。然而這項新工作顯示這正是大腦恢復受損記憶的能力。區別遠大於理論。如果記憶在存儲前就被篡改，那這段記憶就永遠丟失了。但如果利根博士是對的，那段記憶被正確保留在痴呆症患者的大腦裡。意味著有可能通過對人類患者適應光遺傳學來恢復它們。
8But there is a more immediate consequence of the work for the estimated 40m people with the disease. Electrical stimulation of large areas of the brain of Alzheimer’s patients is already being tried, using electrodes implanted in the skull. But Dr Tonegawa’s team found that stimulating neurons in the dentate gyrus other than those directly involved with holding the fear memory prevented Alzheimer’s mice from remembering their shocks in the long term. That suggests that unless the technique can be refined, deep-brain stimulation may not be effective.
但這有一個更直接的調查結果，估計有4千萬人患有痴呆症。用電極植入頭腦裡來對痴呆症病人大腦大區域電刺激也準備好被嘗試。但利根博士的團隊發現刺激齒狀回去神經元而不是保持住害怕記憶，因為這會阻止痴呆症老鼠長時間記憶電擊感受。這說明除非技術能夠進步，深度大腦刺激可能無效。