干細(xì)胞移植有望成為未來疾病治療的一種重要手段，科學(xué)家的設(shè)想是,，利用新轉(zhuǎn)入的干細(xì)胞分化產(chǎn)生新的組織細(xì)胞,，從而彌補(bǔ)和替代機(jī)體的損傷。不過,，美國科學(xué)家的一項(xiàng)最新研究表明,，盡管移植入的一些干細(xì)胞看起來是在“袖手旁觀”，但它們卻能以一種出人意料的途徑發(fā)揮作用,。相關(guān)論文發(fā)表在10月31日的《神經(jīng)科學(xué)雜志》（Journal of Neuroscience）上,。
此前的研究已經(jīng)證實(shí)，干細(xì)胞移植能夠治療小鼠的大腦疾病和損傷,，比如阿爾海默癥,、中風(fēng)等。不過,，利用最新的研究結(jié)果,，美國加州大學(xué)爾灣分校的科學(xué)家推測，神經(jīng)干細(xì)胞能夠挽救小鼠的記憶的作用方式并非人們期望的產(chǎn)生新的大腦組織,，而是通過分泌神經(jīng)營養(yǎng)素蛋白（neurotrophins）來阻止腦細(xì)胞的誘導(dǎo)調(diào)亡,，并加強(qiáng)那些“倒霉”神經(jīng)元間的相互聯(lián)系，從而維持大腦原有的功能,。
領(lǐng)導(dǎo)該項(xiàng)研究的神經(jīng)生物學(xué)教授Frank LaFerla表示,，“這項(xiàng)研究得到的最重要的啟示就是干細(xì)胞能夠挽救由腦細(xì)胞減少導(dǎo)致的記憶損失。”如果這種療效確實(shí)是單純由神經(jīng)營養(yǎng)因子引起的,，那無疑將為修復(fù)大腦記憶和學(xué)習(xí)能力開辟一條陽光大道,。
在研究中，LaFerla小組創(chuàng)造出了海馬區(qū)（大腦與記憶相關(guān)區(qū)域）受損的基因改造小鼠。一項(xiàng)測試表明,，從它們熟悉的籠子中拿走一樣物品,，這些變異小鼠察覺不出來的幾率是正常的同類的兩倍。不過,，當(dāng)研究人員向變異小鼠中海馬區(qū)導(dǎo)入20萬個(gè)干細(xì)胞,，又過了3個(gè)月后發(fā)現(xiàn)，這些變異小鼠的記憶力已經(jīng)與正常的同類相差無幾,。
對照研究表明,，有熒光標(biāo)記的干細(xì)胞在正常小鼠腦中到處散布，而在變異小鼠腦中,，幾乎所有的干細(xì)胞都聚集在海馬區(qū),。LaFerla說，“損傷區(qū)域一定發(fā)出了某種未知信號,，告訴干細(xì)胞要留在這里,。”
此外，更令研究人員驚訝的是,，只有大約5%的干細(xì)胞分化為成熟的神經(jīng)元,。而周圍的神經(jīng)元自始至終一直存在，而且與其他細(xì)胞發(fā)生了更密集的聯(lián)接,。研究人員推測,，這應(yīng)該是干細(xì)胞產(chǎn)生的神經(jīng)營養(yǎng)作用。
研究小組下一步的目標(biāo)就是試圖確定起作用的物質(zhì),。美國耶魯大學(xué)醫(yī)學(xué)院的精神病學(xué)教授Eugene Redmond評價(jià)道,，新的研究進(jìn)行得“相當(dāng)漂亮”。而此次研究的結(jié)論與他的小組在猴子中研究帕金森癥得到的結(jié)論十分相似,。Redmond等人研究發(fā)現(xiàn),，干細(xì)胞移植不僅補(bǔ)充替代了猴腦中缺失的神經(jīng)元，同時(shí)也帶來了其他方面的益處,。（科學(xué)網(wǎng) 任霄鵬/編譯）
原始出處:
The Journal of Neuroscience, April 18, 2007, 27(16):4385-4395; doi:10.1523/JNEUROSCI.0055-07.2007
Dietary Docosahexaenoic Acid and Docosapentaenoic Acid Ameliorate Amyloid-ß and Tau Pathology via a Mechanism Involving Presenilin 1 Levels
Kim N. Green,1 Hilda Martinez-Coria,1 Hasan Khashwji,1 Eileen B. Hall,2 Karin A. Yurko-Mauro,2 Lorie Ellis,2 and Frank M. LaFerla1
1Department of Neurobiology and Behavior, University of California, Irvine, California 92697-4545, and 2Martek Biosciences Corporation, Columbia, Maryland 21045
Correspondence should be addressed to Dr. Frank M. LaFerla, Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Building, Irvine, CA 92697-4545. Email: [email protected]
The underlying cause of sporadic Alzheimer disease (AD) is unknown, but a number of environmental and genetic factors are likely to be involved. One environmental factor that is increasingly being recognized as contributing to brain aging is diet, which has evolved markedly over modern history. Here we show that dietary supplementation with docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, in the 3xTg-AD mouse model of AD reduced the intraneuronal accumulation of both amyloid-ß (Aß) and tau. In contrast, combining DHA with n-6 fatty acids, either arachidonic acid or docosapentaenoic acid (DPAn-6), diminished the efficacy of DHA over a 12 month period. Here we report the novel finding that the mechanism accounting for the reduction in soluble Aß was attributable to a decrease in steady-state levels of presenilin 1, and not to altered processing of the amyloid precursor protein by either the - or ß-secretase. Furthermore, the presence of DPAn-6 in the diet reduced levels of early-stage phospho-tau epitopes, which correlated with a reduction in phosphorylated c-Jun N-terminal kinase, a putative tau kinase. Collectively, these results suggest that DHA and DPAn-6 supplementations could be a beneficial natural therapy for AD.
Key words: tau; Alzheimer's; docosahexanoic acid; docosapentaenoic acid; presenilin; amyloid; transgenic
