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原子力显微镜和体内磁共振弹性成像研究小鼠海马亚区的力学性能。

Mechanical properties of murine hippocampal subregions investigated by atomic force microscopy and in vivo magnetic resonance elastography.

机构信息

Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Institute of Anatomy, University of Leipzig, Leipzig, Germany.

出版信息

Sci Rep. 2022 Oct 6;12(1):16723. doi: 10.1038/s41598-022-21105-7.

Abstract

The hippocampus is a very heterogeneous brain structure with different mechanical properties reflecting its functional variety. In particular, adult neurogenesis in rodent hippocampus has been associated with specific viscoelastic properties in vivo and ex vivo. Here, we study the microscopic mechanical properties of hippocampal subregions using ex vivo atomic force microscopy (AFM) in correlation with the expression of GFP in presence of the nestin promoter, providing a marker of neurogenic activity. We further use magnetic resonance elastography (MRE) to investigate whether in vivo mechanical properties reveal similar spatial patterns, however, on a much coarser scale. AFM showed that tissue stiffness increases with increasing distance from the subgranular zone (p = 0.0069), and that stiffness is 39% lower in GFP than non-GFP regions (p = 0.0004). Consistently, MRE showed that dentate gyrus is, on average, softer than Ammon´s horn (shear wave speed = 3.2 ± 0.2 m/s versus 4.4 ± 0.3 m/s, p = 0.01) with another 3.4% decrease towards the subgranular zone (p = 0.0001). The marked reduction in stiffness measured by AFM in areas of high neurogenic activity is consistent with softer MRE values, indicating the sensitivity of macroscopic mechanical properties in vivo to micromechanical structures as formed by the neurogenic niche of the hippocampus.

摘要

海马体是一个非常异质的脑结构,具有不同的力学特性,反映了其功能的多样性。特别是,啮齿动物海马体中的成年神经发生与体内和体外的特定粘弹性特性有关。在这里,我们使用体外原子力显微镜(AFM)研究海马体亚区的微观力学特性,并与巢蛋白启动子存在下 GFP 的表达相关联,提供神经发生活性的标志物。我们进一步使用磁共振弹性成像(MRE)来研究体内力学特性是否揭示出类似的空间模式,然而,其在更粗糙的尺度上。AFM 显示,组织刚度随距颗粒下层(SGZ)距离的增加而增加(p=0.0069),并且 GFP 区域的刚度比非 GFP 区域低 39%(p=0.0004)。一致地,MRE 显示出齿状回的平均硬度低于 Ammon´s horn(剪切波速度=3.2±0.2 m/s 与 4.4±0.3 m/s,p=0.01),而向 SGZ 方向则降低了 3.4%(p=0.0001)。在具有高神经发生活性的区域中,AFM 测量的刚度明显降低与 MRE 值变软一致,表明体内宏观力学特性对海马体神经发生龛形成的微结构具有敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75fc/9537158/cc49994602c3/41598_2022_21105_Fig1_HTML.jpg

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