Yachnis A T, Giovanini M A, Eskin T A, Reier P J, Anderson D K
Department of Pathology, University of Florida Brain Institute, Gainesville.
Exp Neurol. 1998 Mar;150(1):82-97. doi: 10.1006/exnr.1997.6746.
The cell death suppressors bcl-2 and bcl-x are developmentally regulated and may modulate physiologic cell death in the central nervous system (CNS). However, little data are currently available on the expression patterns of these polypeptides in the human CNS. We examined the ontogeny of bcl-2 and bcl-x in 12 human spinal cords of gestational ages (GA) between 5 and 39 weeks and in 3 adult cords. Paraffin sections were probed by immunohistochemistry using well-characterized, commercially available antibodies that had been raised against poorly conserved epitopes of these homologous proteins. Between 5 and 10 weeks GA, bcl-2 immunoreactivity was identified in primitive neuroepithelial cells of the ventricular zone. Individual cells of the mantle zone were stained including clusters of early anterior horn cells. Bcl-x immunoreactivity was most prominent in differentiating neurons of the mantle zone and less pronounced in the ventricular zone. Between 10 and 14 weeks GA, bcl-2 staining was observed in cells lining the central canal, neurons of the dorsal horn (especially laminae I and II), and in anterior horn cells. The latter exhibited a range of staining intensities from moderate to nondetectable. Bcl-2 immunoreactivity became markedly reduced between 15 and 25 weeks GA, persisting only in ependymal cells. In contrast, strong bcl-x staining was observed in most neurons throughout development and into adulthood. The period of apparent bcl-2 down-regulation overlaps with a peak in physiologic motoneuron death and the establishment of functional neuromuscular synapses in the human spinal cord. These findings suggest that bcl-2 and bcl-x may both be required for survival of early postmitotic neurons before appropriate synaptic connections have been established. Continued neuronal survival (after bcl-2 is down-regulated) may require persistent bcl-x expression in addition to target-derived neurotrophic factors made available through the formation of appropriate synapses.
细胞死亡抑制因子bcl-2和bcl-x受发育调控，可能调节中枢神经系统（CNS）中的生理性细胞死亡。然而，目前关于这些多肽在人类CNS中的表达模式的数据很少。我们检测了12例孕龄（GA）在5至39周的人类脊髓以及3例成人脊髓中bcl-2和bcl-x的个体发生情况。石蜡切片通过免疫组织化学法用针对这些同源蛋白保守性较差的表位制备的、特征明确的市售抗体进行检测。在孕龄5至10周时，在脑室区的原始神经上皮细胞中检测到bcl-2免疫反应性。外套层的单个细胞被染色，包括早期前角细胞簇。bcl-x免疫反应性在外套层分化中的神经元中最为显著，在脑室区则较弱。在孕龄10至14周时，在中央管内衬细胞、背角神经元（尤其是I层和II层）以及前角细胞中观察到bcl-2染色。后者表现出从中等强度到无法检测的一系列染色强度。在孕龄15至25周期间，bcl-2免疫反应性明显降低，仅在室管膜细胞中持续存在。相比之下，在整个发育过程直至成年期，大多数神经元中均观察到强烈的bcl-x染色。bcl-2明显下调的时期与人类脊髓中生理性运动神经元死亡的高峰期以及功能性神经肌肉突触的建立相重叠。这些发现表明，在建立适当的突触连接之前，bcl-2和bcl-x可能都是有丝分裂后早期神经元存活所必需的。除了通过形成适当突触获得的靶源性神经营养因子外，神经元的持续存活（在bcl-2下调后）可能还需要持续的bcl-x表达。
