β淀粉樣肽表達引起軸索線粒體數(shù)量減少但體積增大,，提示線粒體的分裂障礙
1月27日，美國《神經(jīng)科學雜志》（Journal of Neuroscience）發(fā)表了神經(jīng)科學研究所黃福德研究小組及其合作者的最新研究成果――“Expression of β-Amyloid Induced Age-Dependent Presynaptic and Axonal Changes in Drosophila”,。該項工作由神經(jīng)所黃福德小組的趙曉亮，譚江秀,，張瀟,，張保柱，王宇航,，楊程韓宇以及上海交通大學的王文安,，黃健康，朱紅蓮,，孫曉江共同完成,。
阿爾茲海默病（Alzheimer’s Disease,AD）是老年人中最常見的癡呆病,。突觸功能異常和突觸丟失被廣泛認為是AD癡呆癥的細胞機制,，但在AD中突觸結構和功能異常的性質和進程基本未知。通過在特定組織中表達β淀粉樣肽,，作者在成蟲果蠅中建立了一個AD模型,。利用該模型對單個神經(jīng)元的軸索和突觸前的結構和功能進行了大量的時程檢測，發(fā)現(xiàn)β淀粉樣肽表達早期引起突觸前線粒體減少,，可能抑制了線粒體的分裂,，隨后引起一系列其它軸索和突觸前結構與功能的變化。
該項工作得到了中國科學院,、科技部以及上海市政府的項目資助,。（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Neuroscience, January 27, 2010, 30(4):1512-1522; doi:10.1523/JNEUROSCI.3699-09.2010
Expression of β-Amyloid Induced Age-Dependent Presynaptic and Axonal Changes in Drosophila
Xiao-Liang Zhao,1 * Wen-An Wang,2 * Jiang-Xiu Tan,1 Jian-Kang Huang,3 Xiao Zhang,1 Bao-Zhu Zhang,1 Yu-Hang Wang,1 Han-Yu YangCheng,1 Hong-Lian Zhu,3 Xiao-Jiang Sun,3 and Fu-De Huang1
1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, 2Department of Neurology, Xin Hua Hospital affiliated with Shanghai Jiaotong University School of Medicine, Shanghai 200233, China, and 3Department of Neurology, The Sixth People's Hospital affiliated with Shanghai Jiaotong University, Shanghai 200092, China
Alzheimer's disease (AD) is attributable to synapse dysfunction and loss, but the nature and progression of the presynaptic structural and functional changes in AD are essentially unknown. We expressed wild-type or arctic form of β amyloid1-42 (Aβ) in a small group of neurons in the adult fly and performed extensive time course analysis of the function and structure of both axon and presynaptic terminals at the identified single-neuron level. Aβ accumulated intracellularly and induced a range of age-dependent changes, including depletion of presynaptic mitochondria, slowdown of bi-directional transports of axonal mitochondria, decreased synaptic vesicles, increased large vacuoles, and elevated synaptic fatigue. These structural and functional synaptic changes correlated with age-dependent deficit in motor behavior. All these alterations were accelerated in flies expressing the arctic form of Aβ. The depletion of presynaptic mitochondria was the earliest detected phenotype and was not caused by the change in axonal transport of mitochondria. Moreover, axonal mitochondria exhibited a dramatic reduction in number but a significant increase in size in aged Aβ-expressing flies, indicating a global depletion of mitochondria in the neuron and an impairment of mitochondria fission. These results suggest that Aβ accumulation depletes presynaptic and axonal mitochondria, leading to other presynaptic deficits.
