单倍体基因缺陷小鼠前额叶皮层树突棘头直径减小

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Anna K. Cook, Kelsey M. Greathouse, Phaedra N. Manuel, Noelle H. Cooper, Juliana M. Eberhardt, Cameron D. Freeman, Audrey J. Weber, Jeremy H. Herskowitz, Andrew E. Arrant
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引用次数: 0

摘要

前花粉蛋白(GRN)基因的功能缺失突变是导致额颞叶痴呆症(FTD)的常染色体显性病因。这些突变通常会导致原花粉蛋白的单倍体缺乏。Grn+/-小鼠提供了一种原花青素单倍蛋白缺乏的模型,并在 9-10 个月大时出现类似于 FTD 的行为异常。在之前的研究中,我们证明了 Grn+/- 小鼠在试管试验中会出现低支配力表型,这与内侧前额叶皮层(mPFC)前边缘区 II/III 层锥体神经元树突轴化减少有关,而内侧前额叶皮层前边缘区是试管试验中社会支配行为的关键区域。在这项研究中,我们探讨了单倍蛋白缺乏是否会诱发树突棘密度和形态的变化。我们对 9-10 个月大的野生型小鼠或 Grn+/- 小鼠的前边缘 mPFC 中的单个 II/III 层锥体神经元进行了荧光染料离子显微注射,然后用高分辨率共聚焦显微镜和三维重建技术进行了形态学分析。Grn+/-小鼠的树突棘密度与野生型同窝小鼠相当,但Grn+/-小鼠的顶端树突棘类型比例发生了变化,粗棘减少,细棘增多。此外,与野生型小鼠相比,Grn+/-小鼠的顶端树突具有更长的棘突和更小的细棘突头直径。脊柱形态的这些变化可能是导致Grn+/-小鼠回路级活动改变和社会优势缺陷的原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dendritic spine head diameter is reduced in the prefrontal cortex of progranulin haploinsufficient mice
Loss-of-function mutations in the progranulin (GRN) gene are an autosomal dominant cause of Frontotemporal Dementia (FTD). These mutations typically result in haploinsufficiency of the progranulin protein. Grn+/– mice provide a model for progranulin haploinsufficiency and develop FTD-like behavioral abnormalities by 9–10 months of age. In previous work, we demonstrated that Grn+/– mice develop a low dominance phenotype in the tube test that is associated with reduced dendritic arborization of layer II/III pyramidal neurons in the prelimbic region of the medial prefrontal cortex (mPFC), a region key for social dominance behavior in the tube test assay. In this study, we investigated whether progranulin haploinsufficiency induced changes in dendritic spine density and morphology. Individual layer II/III pyramidal neurons in the prelimbic mPFC of 9–10 month old wild-type or Grn+/– mice were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and 3D reconstruction for morphometry analysis. Dendritic spine density in Grn+/– mice was comparable to wild-type littermates, but the apical dendrites in Grn+/– mice had a shift in the proportion of spine types, with fewer stubby spines and more thin spines. Additionally, apical dendrites of Grn+/– mice had longer spines and smaller thin spine head diameter in comparison to wild-type littermates. These changes in spine morphology may contribute to altered circuit-level activity and social dominance deficits in Grn+/– mice.
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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