DeLuca G C, Nagy Zs, Esiri M M, Davey P
Department of Neuropathology and Clinical Neurology, Radcliffe Infirmary, Oxford OX2 6HE, UK.
Acta Neuropathol. 2002 Jun;103(6):590-8. doi: 10.1007/s00401-001-0508-2. Epub 2002 Feb 15.
We have performed an immunocytochemical study of autopsy material from five cases of central pontine myelinolysis (CPM) and five age and sex-matched control subjects with the aim of exploring the possible involvement of apoptotic mechanisms in oligodendrocytes in this condition. We searched for immunoreactivity of glial cells for the apoptotic-related markers death receptor (DR) 3, Bax and Bak, the anti-apoptotic marker Bcl-2 and the cell cycle marker Ki-67. The latter marker was studied because it is known that entry of cells into the cell division cycle can trigger apoptosis if it does not result in mitosis. In CPM there was marked up-regulation of expression of the myelination-related enzyme carbonic anhydrase isoenzyme II and also markedly increased expression of Ki-67 in nuclei of glial cells of all types but particularly those of cells morphologically resembling oligodendrocytes. Despite this, there was no clear increase in density of such cells in CPM. The pro-apoptotic markers Bax, Bak and DR3 were all modestly increased in glial cell cytoplasm in CPM, while there was no change in expression of Bcl-2, which was only sparsely detected in glial cells both in controls and cases of CPM. The ratio of pro- to anti-apoptotic factors would appear from this evidence to have altered in favour of apoptosis in glial cells, most of which had the appearance of oligodendrocytes and many of which expressed Ki-67. We interpret this preliminary study as favouring apoptosis as a mechanism of oligodendrocytic death in CPM. Further study of this mechanism in CPM may lead to identification of factors that could reduce or prevent this rare but serious and often fatal disease.
我们对5例中央桥脑髓鞘溶解症（CPM）尸检材料以及5例年龄和性别匹配的对照者进行了免疫细胞化学研究，目的是探讨这种情况下少突胶质细胞凋亡机制的可能参与情况。我们检测了神经胶质细胞对凋亡相关标志物死亡受体（DR）3、Bax和Bak、抗凋亡标志物Bcl-2以及细胞周期标志物Ki-67的免疫反应性。之所以研究后一种标志物，是因为已知细胞进入细胞分裂周期如果不导致有丝分裂就会触发凋亡。在CPM中，髓鞘形成相关酶碳酸酐酶同工酶II的表达明显上调，并且所有类型神经胶质细胞核中Ki-67的表达也明显增加，尤其是形态上类似少突胶质细胞的那些细胞。尽管如此，CPM中这类细胞的密度并没有明显增加。促凋亡标志物Bax、Bak和DR3在CPM神经胶质细胞质中均有适度增加，而Bcl-2的表达没有变化，在对照组和CPM病例的神经胶质细胞中均仅少量检测到。从这一证据来看，促凋亡与抗凋亡因子的比例似乎发生了变化，有利于神经胶质细胞凋亡，其中大多数细胞具有少突胶质细胞的外观，许多细胞表达Ki-67。我们将这项初步研究解释为支持凋亡是CPM中少突胶质细胞死亡的一种机制。对CPM中这种机制的进一步研究可能会导致识别出可以减轻或预防这种罕见但严重且往往致命疾病的因素。
