Gleckman A M, Jiang Z, Liu Y, Smith T W
Department of Pathology (Neuropathology), University of Massachusetts Medical School, Worcester 01655-0125, USA.
Acta Neuropathol. 1999 Jul;98(1):55-61. doi: 10.1007/s004010051051.
Pick's disease (PD) is characterized by severe neuronal loss and gliosis in a frontotemporal lobar distribution, often associated with Pick bodies and ballooned neurons. Abnormal tau metabolism has been implicated in the pathogenesis of PD; however, the underlying mechanism of neuronal degeneration remains poorly understood. Evidence from other neurodegenerative diseases has suggested that DNA damage and apoptosis may play a major role in cellular degeneration and death. In the present study, an in situ nucleotidyl transferase assay (ISNTA) was used to identify DNA fragmentation in three cases of classical PD with Pick bodies and ballooned neurons, and two PD "variants", one with ballooned neurons only and the other without Pick bodies or ballooned neurons. In all cases large numbers of ISNTA-positive neurons were present in anatomic regions having obvious degenerative changes (neuronal atrophy and loss, gliosis, cytoplasmic inclusions) by conventional histology. There was no clear association between neuronal DNA fragmentation and the presence of structural abnormalities such as Pick bodies or ballooned cytoplasm. ISNTA-positive glia were present in both cortex and subcortical white matter. Morphologic evidence of apoptosis was not detected in either neurons or glial cells. We suggest that DNA fragmentation in PD and probably other neurodegenerative disorders most likely specifies a population of potentially vulnerable cells in which both cell death and repair mechanisms have been activated. It is likely that only a very small number of these vulnerable cells at a given time will proceed to cell death; however, it is uncertain whether this occurs by apoptosis or some other mechanism.
匹克氏病（PD）的特征是额颞叶区域出现严重的神经元丢失和胶质细胞增生，常伴有匹克小体和气球样神经元。异常的tau蛋白代谢与PD的发病机制有关；然而，神经元变性的潜在机制仍知之甚少。来自其他神经退行性疾病的证据表明，DNA损伤和细胞凋亡可能在细胞变性和死亡中起主要作用。在本研究中，采用原位核苷酸转移酶测定法（ISNTA）来鉴定3例具有匹克小体和气球样神经元的经典PD以及2例PD“变异型”（1例仅具有气球样神经元，另1例既无匹克小体也无气球样神经元）中的DNA片段化情况。在所有病例中，通过传统组织学检查发现，在具有明显退行性改变（神经元萎缩和丢失、胶质细胞增生、胞质内包涵体）的解剖区域存在大量ISNTA阳性神经元。神经元DNA片段化与诸如匹克小体或气球样细胞质等结构异常的存在之间没有明显关联。皮质和皮质下白质中均存在ISNTA阳性胶质细胞。在神经元或胶质细胞中均未检测到细胞凋亡的形态学证据。我们认为，PD以及可能其他神经退行性疾病中的DNA片段化很可能确定了一群潜在易损细胞，其中细胞死亡和修复机制均已被激活。很可能在给定时间只有极少数这些易损细胞会走向细胞死亡；然而，尚不确定这是通过细胞凋亡还是其他某种机制发生的。
