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整倍体和16三体小鼠基底前脑的神经发生:唐氏综合征发育障碍的动物模型。

Neurogenesis of the basal forebrain in euploid and trisomy 16 mice: an animal model for developmental disorders in Down syndrome.

作者信息

Sweeney J E, Höhmann C F, Oster-Granite M L, Coyle J T

机构信息

Department of Environmental Health Sciences, Johns Hopkins University Medical Institutions, Baltimore, MD 21205.

出版信息

Neuroscience. 1989;31(2):413-25. doi: 10.1016/0306-4522(89)90384-9.

DOI:10.1016/0306-4522(89)90384-9
PMID:2529451
Abstract

The neurogenesis and early histochemical differentiation of the basal forebrain in trisomy 16 fetal mice and their euploid littermates were examined by combining [3H]thymidine autoradiography with acetylcholinesterase histochemistry. Neurons of the basal forebrain were being born between embryonic day 11 and 15 in both chromosomally normal (euploid) and aneuploid mice. In euploid littermate controls, neurogenesis proceeded along a caudal to rostral gradient with the peak on embryonic day 11 for caudal portions and embryonic day 13 for rostral portions of the basal forebrain. In contrast, in trisomy 16 mice, rostral sections exhibited a peak of neurogenesis on embryonic day 11, 2 days earlier than in their euploid littermate controls. Hypocellularity of the basal forebrain region was noted in trisomy 16 mice; particularly dramatic was the reduction of the population of cells that expressed acetylcholinesterase. This reduction in cell number in the trisomics was not accompanied by a reduction in cell size or by a dramatic change in the distribution of residual neurons when compared to that of euploid littermate controls. Since trisomy 16 mice do not survive the perinatal period, we examined the pattern of acetylcholinesterase expression in normal C57B1/6J mice from embryonic day 16 to postnatal day 5 to determine the postnatal disposition of these neurons. Already at embryonic day 16, fibers staining for acetylcholinesterase penetrated the striatal anlage, in their course towards targets in the cerebral cortices. By postnatal day 5, the previously expansive distribution of basal forebrain neurons had become consolidated in a more ventral and rostral position by the extensive outgrowth of the striatal neurons, a pattern resembling that seen in adult animals.

摘要

通过将[3H]胸腺嘧啶核苷放射自显影术与乙酰胆碱酯酶组织化学相结合,研究了16三体胎儿小鼠及其正常二倍体同窝小鼠基底前脑的神经发生和早期组织化学分化。在染色体正常(二倍体)和非整倍体小鼠中,基底前脑的神经元均在胚胎第11天至15天之间产生。在正常二倍体同窝对照中,神经发生沿尾侧至头侧梯度进行,基底前脑尾侧部分在胚胎第11天达到峰值,头侧部分在胚胎第13天达到峰值。相比之下,在16三体小鼠中,头侧切片在胚胎第11天出现神经发生峰值,比其正常二倍体同窝对照早2天。在16三体小鼠中观察到基底前脑区域细胞减少;尤其显著的是表达乙酰胆碱酯酶的细胞数量减少。与正常二倍体同窝对照相比,三体小鼠中细胞数量的减少并未伴随着细胞大小的减小或残留神经元分布的显著变化。由于16三体小鼠在围产期无法存活,我们检查了正常C57B1/6J小鼠从胚胎第16天到出生后第5天的乙酰胆碱酯酶表达模式,以确定这些神经元的出生后分布。在胚胎第16天,乙酰胆碱酯酶染色的纤维就已穿透纹状体原基,向大脑皮质的靶点延伸。到出生后第5天,基底前脑神经元先前广泛的分布已通过纹状体神经元的广泛生长而巩固在更腹侧和头侧的位置,这种模式类似于成年动物中所见的模式。

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