Sarnat Harvey B, Resch Lothar, Flores-Sarnat Laura, Yu Weiming
Department of Paediatrics, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Department of Pathology (Neuropathology), University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Department of Clinical Neurosciences, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
Department of Pathology (Neuropathology), University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
Brain Dev. 2014 Jun;36(6):463-71. doi: 10.1016/j.braindev.2014.01.008. Epub 2014 Feb 14.
Genetic programming of cerebral development involves tissue morphogenesis and also timing of developmental processes. Precocious synaptogenesis in the neocortical plate was previously demonstrated in 5 of 6 fetuses of 20-31 weeks gestation.
Neuropathological examination was performed of a 13-week-5-day fetus with trisomy-13, a lobar holoprosencephaly, hydrocephalus, cyclopia and absence of ears. Immunocytochemical demonstration of the synaptic vesicle protein synaptophysin was performed in the brain and retina, along with other neuronal markers.
Synaptophysin reactivity in the cortical plate was patchy and precocious. Radial glial fibres, demonstrated by vimentin, were oriented parallel to the cortical plate rather than perpendicular, probably because of hydrocephalus. A corpus striatum was not identified, but the poorly formed thalamus exhibited synaptophysin reactivity around many neurones. The cyclopean eye had ocular features of maturational delay including persistent hyaloid artery; ganglion cells were reduced in number, but retinal synaptophysin reactivity was paradoxically precocious.
Holoprosencephaly exhibits abnormal patchy synapse distribution in the neocortex and retina; synaptogenesis was precocious, as we previously described in older fetuses. Too soon an onset of synapse formation may promote early epileptic circuitry, leading to severe infantile epilepsies postnatally. The visual system is the last of the special sensory systems to mature, yet in this case showed too early synapse formation. In HPE, cyclopia and in trisomy 13, total absence of external ears has not been reported; it results from faulty craniofacial induction by neural crest.
大脑发育的基因编程涉及组织形态发生以及发育过程的时间安排。先前在妊娠20 - 31周的6例胎儿中的5例中证实了新皮质板中突触发生过早。
对一名孕13周5天、患有13 -三体综合征、叶型前脑无裂畸形、脑积水、独眼畸形且无耳的胎儿进行神经病理学检查。在脑和视网膜中进行了突触小泡蛋白突触素的免疫细胞化学检测，以及其他神经元标志物的检测。
皮质板中的突触素反应呈斑片状且过早出现。波形蛋白显示的放射状胶质纤维与皮质板平行而非垂直排列，可能是由于脑积水所致。未发现纹状体，但发育不良的丘脑在许多神经元周围表现出突触素反应。独眼具有成熟延迟的眼部特征，包括持续存在的玻璃体动脉；神经节细胞数量减少，但视网膜突触素反应却异常早熟。
前脑无裂畸形在新皮质和视网膜中表现出异常的斑片状突触分布；突触发生过早，正如我们之前在较大胎儿中所描述的那样。突触形成过早可能会促进早期癫痫环路的形成，导致出生后严重的婴儿癫痫。视觉系统是最后成熟的特殊感觉系统，但在这种情况下却显示出过早的突触形成。在前脑无裂畸形、独眼畸形和13 -三体综合征中，完全没有外耳的情况尚未见报道；这是由神经嵴对颅面诱导异常所致。
