Attenuated Nuclear Shrinkage in Neurons with Nuclear Aggregates— A Morphometric Study on Pontine Neurons of Machado–Joseph Disease Brains
Attenuated Nuclear Shrinkage in Neurons with Nuclear Aggregates— A Morphometric Study on Pontine Neurons of Machado–Joseph Disease Brains
复制标题
核聚集减弱神经元的核收缩——马查多-约瑟夫病脑桥神经元的形态测量研究
DOI：
10.1006/exnr.2002.8028
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发表时间：
2002
影响因子：
5.3
通讯作者：
S. Yagishita
中科院分区：
文献类型：
--
作者：
T. Uchihara;K. Iwabuchi;N. Funata;S. Yagishita
Machado-Joseph病（MJD）患者大脑中的核聚集体（NAs）和神经退行性变都是由ataxin-3中CAG/polyglutamine repeat的病理扩增引发的，但NA的形成是否与加速的神经退行性变有关仍有待澄清。为了阐明NAs对人脑神经元的可能影响，我们量化了4名MJD患者和5名对照者尸检脑的桥脑准备横截面上神经元核的大小和畸形（分别有或没有NAs）。与对照组相比，MJD大脑的核萎缩和畸形更为明显，而这些变化在含有NAs的神经元中减弱。MJD的NAs可能与一种减缓而不是加速核萎缩和畸形的机制有关。这一发现使我们考虑到NAs不一定对患病人脑中的神经元有毒。
Nuclear aggregates (NAs) and neurodegeneration in brains from patients with Machado-Joseph disease (MJD) are both triggered by pathological expansion of CAG/polyglutamine repeat in ataxin-3, but it remains to be clarified whether NA formation is associated with accelerated neurodegeneration. In an attempt to clarify a possible influence of NAs on neurons in human brains, we quantified the size and deformity of neuronal nuclei (those with or without NAs, separately) cross-sectioned on pontine preparations of autopsied brains from four patients with MJD and five controls. Nuclear shrinkage and deformity were more marked in MJD brains than in controls, and these changes were attenuated in neurons harboring NAs. NAs of MJD are presumably linked to a mechanism that attenuates rather than accelerates nuclear shrinkage and deformity. This finding leads us to consider that NAs are not necessarily toxic to neurons in diseased human brains.