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视网膜变性小鼠视觉皮层的出生后早期发育

Early postnatal development of the visual cortex in mice with retinal degeneration.

作者信息

Himmelhan D K, Rawashdeh O, Oelschläger H H A

机构信息

Department of Anatomy III (Dr. Senckenbergische Anatomie), Johann Wolfgang Goethe University, Frankfurt am Main, Germany.

Department of Anatomy III (Dr. Senckenbergische Anatomie), Johann Wolfgang Goethe University, Frankfurt am Main, Germany; School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.

出版信息

Mech Dev. 2018 Jun;151:1-9. doi: 10.1016/j.mod.2018.03.002. Epub 2018 Mar 19.

Abstract

This study characterizes the early postnatal development of the visual neocortex in C3H/HeNRj mice. These mice are homozygous for the Pde6b mutation, which causes retinal degeneration starting from postnatal day 7 (P7). To monitor the development of the visual cortex between P3 and P28 we used eight antigens known to be expressed at different developmental stages (Nestin, tau3, β3- Tubulin, Calbindin, Doublecortin, MAP2, Parvalbumin and NeuN). Using semiquantitative analysis we traced the expression and localization of different developmental markers throughout the layers of the visual cortex. Cortical tissue sections corresponding to the first postnatal week (P3-P6) stained positively for Nestin, tau3, β3-Tubulin and Calbindin. These proteins are known to be involved in the migration of neural progenitor cells (NPCs) within the cortical plate. At the time of eye-opening (P14), Doublecortin, MAP2 and NeuN, markers for developing and maturing neurons involved in NPC differentiation are present. Between P9 and P21 Nestin and Calbindin disappear while NeuN and Parvalbumin expression increases in the course of visual neocortex development. The findings of this study provide a snapshot of the dynamic changes in cortex formation during early postnatal development. So far, it is the first investigation on the postnatal development of the mouse visual cortex. Our results indicate that in C3H/HeNRj mice retinal degeneration during these early stages may not influence the maturation of the visual cortex. Until P28 in this mouse strain, the development of the visual neocortex is in accordance with data from other mice (C57BL/6) without retinal degeneration. Whether in older individuals of the C3H/HeNRj strain the visual neocortex will show signs of functional impairment has to be shown by future work.

摘要

本研究描述了C3H/HeNRj小鼠视觉新皮质出生后的早期发育情况。这些小鼠为Pde6b突变的纯合子,该突变导致从出生后第7天(P7)开始视网膜退化。为监测P3至P28期间视觉皮质的发育,我们使用了已知在不同发育阶段表达的8种抗原(巢蛋白、tau3、β3微管蛋白、钙结合蛋白、双皮质素、微管相关蛋白2、小白蛋白和神经元核抗原)。通过半定量分析,我们追踪了不同发育标志物在视觉皮质各层的表达和定位。对应于出生后第一周(P3 - P6)的皮质组织切片对巢蛋白、tau3、β3微管蛋白和钙结合蛋白呈阳性染色。已知这些蛋白质参与神经祖细胞(NPCs)在皮质板内的迁移。在睁眼时(P14),出现了双皮质素、微管相关蛋白2和神经元核抗原,它们是参与NPC分化的发育中和成熟神经元的标志物。在P9至P21期间,巢蛋白和钙结合蛋白消失,而在视觉新皮质发育过程中,神经元核抗原和小白蛋白的表达增加。本研究结果提供了出生后早期发育过程中皮质形成动态变化的一个快照。到目前为止,这是对小鼠视觉皮质出生后发育的首次研究。我们的结果表明,在C3H/HeNRj小鼠中,这些早期阶段的视网膜退化可能不会影响视觉皮质的成熟。在该小鼠品系中直到P28,视觉新皮质的发育与其他无视网膜退化的小鼠(C57BL/6)的数据一致。C3H/HeNRj品系年龄较大的个体中视觉新皮质是否会出现功能受损的迹象,还有待未来的研究来证实。

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