The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons.
The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons.
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DOI：
10.1186/1750-1326-9-17
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发表时间：
2014-05-03
影响因子：
15.1
通讯作者：
O'Malley KL
中科院分区：
文献类型：
--
作者：
Lu X;Kim-Han JS;Harmon S;Sakiyama-Elbert SE;O'Malley KL
6-羟基多巴胺（6-OHDA）是帕金森病中多巴胺能（DA）神经元退化最常用的毒素之一。6-羟色胺还会引起轴突变性，这一过程似乎先于DA神经元的死亡。为了了解6-羟多巴胺介导的轴突变性所涉及的过程，设计了一种微装置，用于从细胞体中流体分离轴突，并与绿色荧光蛋白（GFP）标记的DA神经元结合使用。结果表明，6-OHDA可快速诱导DA和非DA轴突线粒体运输功能障碍。这似乎是对运输功能的一般影响，因为6-OHDA也破坏了突触素标记的囊泡的运输。6-OHDA对线粒体运输的影响被sod1 -拟物Mn(III)tetrakis（4-苯甲酸）porphyrin chloride （MnTBAP）以及抗氧化剂n -乙酰半胱氨酸（NAC）的加入所阻断，这表明自由基物种在这一过程中发挥了作用。在时间上，微管破坏和自噬发生在运输功能障碍之后，但在6-OHDA治疗后DA细胞死亡之前。本研究结果提示，6-OHDA治疗后，ros介导的转运功能障碍发生较早，在诱导轴突变性中起重要作用。
6-hydroxydopamine (6-OHDA) is one of the most commonly used toxins for modeling degeneration of dopaminergic (DA) neurons in Parkinson's disease. 6-OHDA also causes axonal degeneration, a process that appears to precede the death of DA neurons. To understand the processes involved in 6-OHDA-mediated axonal degeneration, a microdevice designed to isolate axons fluidically from cell bodies was used in conjunction with green fluorescent protein (GFP)-labeled DA neurons. Results showed that 6-OHDA quickly induced mitochondrial transport dysfunction in both DA and non-DA axons. This appeared to be a general effect on transport function since 6-OHDA also disrupted transport of synaptophysin-tagged vesicles. The effects of 6-OHDA on mitochondrial transport were blocked by the addition of the SOD1-mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), as well as the anti-oxidant N-acetyl-cysteine (NAC) suggesting that free radical species played a role in this process. Temporally, microtubule disruption and autophagy occurred after transport dysfunction yet before DA cell death following 6-OHDA treatment. The results from the study suggest that ROS-mediated transport dysfunction occurs early and plays a significant role in inducing axonal degeneration in response to 6-OHDA treatment.
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影响因子：
4.7
作者：
Cheng HC;Burke RE
通讯作者：
Burke RE
影响因子：
25
作者：
Li, Yanping;Liu, Wencheng;Oo, Tinmarla F.;Wang, Lei;Tang, Yi;Jackson-Lewis, Vernice;Zhou, Chun;Geghman, Kindiya;Bogdanov, Mikhail;Przedborski, Serge;Beal, M. Flint;Burke, Robert E.;Li, Chenjian
通讯作者：
Li, Chenjian
影响因子：
15.1
作者：
Bernstein AI;Garrison SP;Zambetti GP;O'Malley KL
通讯作者：
O'Malley KL
影响因子：
6.6
作者：
Kim-Han, Jeong Sook;O'Malley, Karen L.
通讯作者：
O'Malley, Karen L.
DOI：
10.1523/jneurosci.5519-10.2011
发表时间：
2011-02-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cheng HC;Kim SR;Oo TF;Kareva T;Yarygina O;Rzhetskaya M;Wang C;During M;Talloczy Z;Tanaka K;Komatsu M;Kobayashi K;Okano H;Kholodilov N;Burke RE
通讯作者：
Burke RE