Spremo-Potparević Biljana, Zivković Lada, Djelić Ninoslav, Plećas-Solarović Bosiljka, Smith Mark A, Bajić Vladan
Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
J Neurochem. 2008 Sep;106(5):2218-23. doi: 10.1111/j.1471-4159.2008.05555.x. Epub 2008 Jul 9.
Premature centromere division (PCD) represents a loss of control over the sequential separation and segregation of chromosome centromeres. Although first described in aging women, PCD on the X chromosome (PCD,X) is markedly elevated in peripheral blood lymphocytes of individuals suffering from Alzheimer disease (AD). The present study evaluated PCD,X, using a fluorescent in situ hybridization method, in interphase nuclei of frontal cerebral cortex neurons from sporadic AD patients and age-matched controls. The average frequency of PCD,X in AD patients (8.60 +/- 1.20%) was almost three times higher (p < 0.01) than in the control group (2.96 +/- 1.20). However, consistent with previous studies, no mitotic cells were found in neurons in either AD or control brain, suggesting an intrinsic inability of post-mitotic neurons to divide. In view of the fact that it has been well-documented that neurons in AD can re-enter into the cell division cycle, the findings presented here of increased PCD advance the hypothesis that deregulation of the cell cycle may contribute to neuronal degeneration and subsequent cognitive deficits in AD.
早熟着丝粒分裂(PCD)代表着对染色体着丝粒顺序分离和分离的控制丧失。尽管最早在老年女性中被描述,但X染色体上的PCD(PCD,X)在阿尔茨海默病(AD)患者的外周血淋巴细胞中显著升高。本研究采用荧光原位杂交方法,评估散发性AD患者和年龄匹配对照者额叶大脑皮质神经元间期核中的PCD,X。AD患者中PCD,X的平均频率(8.60 +/- 1.20%)几乎是对照组(2.96 +/- 1.20)的三倍(p < 0.01)。然而,与先前的研究一致,在AD或对照大脑的神经元中均未发现有丝分裂细胞,这表明有丝分裂后神经元内在的分裂无能。鉴于有充分的文献记载AD中的神经元可重新进入细胞分裂周期,此处呈现的PCD增加的发现推进了这样一种假说,即细胞周期失调可能导致AD中的神经元变性及随后的认知缺陷。