科學家首次 '即時的' 看到腦神經的發育狀況


Scientist Observes Brain Cell Development In 'Real Time'



Science Daily — 來自耶路撒冷希伯來大學(Hebrew University of Jerusalem)的研究人員首次在哺乳動物生物體內觀察到腦中神經細胞的生長狀況。



圖1. Magnified photo shows division of neuron in vivo. (Credit: Hebrew University of Jerusalem)


在希伯來大學生活科學 Alexander Silberman 研究所的神經生物學系從事研究工作的 Adi Mizrahi 博士他使用小鼠模型來從事神經元或神經細胞的研究,並針對這些神經相關細胞是如何從一個未分化的細胞變成具豐富且多元的複雜細胞。這個研究具有相當重要的意義,尤其是對於腦部的研究。Mizrahi 博士這樣說到:「有關神經細胞所具有的結構以及功能的複雜性仍舊是神經科學領域中最大的迷團,而我們現在有了一個可以針對此領域進行研究的最直接地模型。」



圖2. Figure 1 Experimental model for in vivo imaging of adult-born neurons.(a) Schematic representation of the mouse brain and the experimental protocol. Injections were targeted to the subventricular zone (SVZ) and imaging was carried out at different times after injections, using two-photon imaging (2PI). (b) A montage of epifluorescent micrographs (10x magnification) from a sagittal brain slice of a brain injected 10 d earlier (Ctx., cortex; OB, olfactory bulb). Scale bar, 500 mm. (c–e) Enlarged images that correspond to the boxed regions in b: injection site (c), RMS (d) and olfactory bulb (e). Images show GFP-expressing cells. Scale bar, 100 um.(圖片來源:Nature Neuroscience, 2007, 10, 444. Fig. 1)



使用特殊的顯微顯影技術,同時配合病毒基因技術,Mizrahi 博士成功的開發出一個可以在生物體內研究神經樹突(neural dendrites)發育的實驗模型。由神經元所延伸出來的類似分支狀的樹突會伸展開來並接觸到另一個神經元,並且扮演著神經元彼此間溝通的角色。

Mizrahi 博士在他的研究中所使用的模型是利用將新出生的神經元發展進入成鼠大腦中掌控嗅覺的嗅球(olfactory bulb)部位,使其成為能提供嗅覺的感知。



圖3. 大腦中掌管嗅覺的「嗅覺球(olfactory bulb)」相關位置(圖片來源:http://cwx.prenhall.com/bookbind/pubbooks/morris2/chapter3/medialib/summary/3.html



圖4. 嗅覺系統(Olfactory System)細部部位名稱(圖片來源:http://flavor.monell.org/~loweg/OlfactoryBulb.htm


透過影像延遲技術,便可以觀察到這些新生的神經元之發展與維護在數天後所產生的不同階段狀態。Mizrahi 表示,神經樹突的形成是高度動態(highly dynamic)的。而且根據研究顯示,一旦合併連結成網路,即便是已經成熟的神經元依舊會維持高度地動態而且依舊保有持續改變的能力。



圖5. Dendrites of spiny PGNs are stable but their spines are dynamic.(a,b) Average intensity projection images from five reconstructions of newborn spiny PGNs (12-h intervals) at 10–12 d.p.i. (a) and 14–16 d.p.i. (b). Images were aligned at the cell body, and for clarity the spines were digitally omitted from the dendrites. Color scale bar indicates how many times a process was located in a given region (from 1 to 5). Bright and dark colors represent stable and dynamic dendrites, respectively. Scale bars, 25 um. (c) Four projection images of the neuron in b (12-hr intervals). Images are maximum projections of the original z stacks. (d) Higher magnification images of a dendritic segment from the spiny dendrite shown in c (boxed regions in c correspond to these segments). Left, spiny dendrite from 14 d.p.i. Center, same spiny dendrite 36 h later. Right, merged image. New spines and a lost spine are highlighted with closed arrowheads and an open arrowhead, respectively.(圖片來源:Nature Neuroscience, 2007, 10, 444. Fig. 5)


這個模型提供了一個可以進行觀察的機轉,這是第一次能針對哺乳動物去觀察神經元是如何發展成為一個豐富且複雜的細胞,以及他是如何發育的,同時也能讓我們去觀察這些神經元是如何保持高度的活性並且不斷地跟著腦中的環境而改變。

如果能繼續的研究下去,也許有一天,我們便可以針對許多與神經元相關疾病的治療進行重要的突破,Mizrahi 博士補充到「在腦中只有屈指可數的區域具有神經細胞新生(neurogenesis)的能力,我們就是要去揭發躲在這些區域當中的秘密!」

The results of Dr. Mizrahi's work appeared in the online edition of Nature Neuroscience.


Note: This story has been adapted from a news release issued by The Hebrew University of Jerusalem.


原始報導:
ScienceDaily:Scientist Observes Brain Cell Development In 'Real Time'


原始論文:
"Dendritic development and plasticity of adult-born neurons in the mouse olfactory bulb", Adi Mizrahi
Nature Neuroscience, 2007, 10, 444.
Published online: 18 March 2007 | doi:10.1038/nn1875
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