Departments of Paediatrics, Pathology (Neuropathology), and Clinical Neurosciences, University of Calgary Faculty of Medicine and Alberta Children's Hospital, Alberta, Canada.
J Neuropathol Exp Neurol. 2010 Mar;69(3):234-45. doi: 10.1097/NEN.0b013e3181d0151f.
To assess the synaptic vesicle protein synaptophysin as a potential marker for maturation in the human fetal brain, synaptophysin immunoreactivity (sIR) was prospectively studied in postmortem sections of 162 normal human fetal and neonatal brains of both sexes from 6 to 41 weeks' gestational age. There was a consistent temporal and spatial pattern of sIR in the hippocampus and cerebral neocortex. In the rostral hippocampus, sIR was first apparent in the molecular zone of the dentate gyrus at 12 weeks, followed by CA2 at 14 weeks, CA3 and CA4 at 15 to 16 weeks, and CA1 at 19 weeks; it was incomplete until 26 weeks. In frontal neocortex, sIR developed in a laminar pattern above and below the cortical plate as early as 12 weeks, around Cajal-Retzius neurons of the molecular zone at 14 weeks, surrounding pyramidal neurons of Layers 5 and 6 at 16 weeks, and at the surface of neuronal somata in Layers 2 and 4 at 22 weeks. At 33 weeks, Layers 2 and 4 still had less sIR than other layers. Uniform sIR among all cortical layers was evident at 38 weeks. Ascending probable thalamocortical axons were reactive as early as 12 weeks and were best demonstrated by 26 weeks, after which increasing sIR in the neuropil diminished the contrast. The sIR was preserved for more than 96 hours postmortem, even in severely autolytic brains. We conclude that synaptophysin is a reliable marker in human fetal brain and that sIR provides the means for objective assessment of cerebral maturation in normal brains and to enable interpretation of abnormal synaptic patterns in pathological conditions.
为了评估突触小泡蛋白突触素是否可以作为人类胎儿大脑成熟的潜在标志物，我们前瞻性地研究了 162 例正常胎儿和新生儿大脑死后标本的突触素免疫反应（sIR），这些标本来自于 6 至 41 孕周的胎儿和新生儿，其性别不限。在海马体和大脑新皮层中，sIR 呈现出一致的时空分布模式。在前脑的海马体中，sIR 最早于 12 周在齿状回的分子层中出现，随后在 14 周时出现在 CA2 区，在 15 至 16 周时出现在 CA3 和 CA4 区，在 19 周时出现在 CA1 区；直到 26 周时，sIR 仍未完全出现。在额皮质中，sIR 最早于 12 周在皮质板上方和下方的层状结构中出现，于 14 周时出现在分子层的 Cajal-Retzius 神经元周围，于 16 周时出现在第 5 和第 6 层的锥体细胞周围，于 22 周时出现在神经元胞体的表面。到 33 周时，第 2 和第 4 层的 sIR 仍少于其他层。到 38 周时，所有皮质层之间的 sIR 均匀一致。向上的可能丘脑皮质轴突最早于 12 周出现反应，在 26 周时反应最佳，此后神经胶质中的 sIR 增加，降低了对比度。sIR 在死后超过 96 小时仍能保存，即使在严重自溶的大脑中也是如此。我们的结论是，突触素是人类胎儿大脑中的可靠标志物，sIR 为客观评估正常大脑的大脑成熟度提供了手段，并使解释病理性异常突触模式成为可能。
