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磁共振弹性成像研究在小鼠模型中淀粉样斑块积累的影响。

Magnetic resonance elastography to study the effect of amyloid plaque accumulation in a mouse model.

机构信息

Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Harvard Medical School, Boston, Massachusetts, USA.

出版信息

J Neuroimaging. 2022 Jul;32(4):617-628. doi: 10.1111/jon.12996. Epub 2022 Apr 5.

Abstract

BACKGROUND AND PURPOSE

Biomechanical changes in the brain have not been fully elucidated in Alzheimer's disease (AD). We aimed to investigate the effect of β-amyloid accumulation on mouse brain viscoelasticity.

METHODS

Magnetic resonance elastography was used to calculate magnitude of the viscoelastic modulus (|G*|), elasticity (G ), and viscosity (G ) in the whole brain parenchyma (WB) and bilateral hippocampi of 9 transgenic J20 (AD) mice (5 males/4 females) and 10 wild-type (WT) C57BL/6 mice (5 males/5 females) at 11 and 14 months of age.

RESULTS

Cross-sectional analyses showed no significant difference between AD and WT mice at either timepoints. No sex-specific differences were observed at 11 months of age, but AD females showed significantly higher hippocampal |G*| and G and WB |G*|, G , and G compared to both AD and WT males at 14 months of age. Similar trending differences were found between female AD and female WT animals but did not reach significance. Longitudinal analyses showed significant increases in hippocampal |G*|, G , and G , and significant decreases in WB |G*|, G , and G between 11 and 14 months in both AD and WT mice. Each subgroup showed significant increases in all hippocampal and significant decreases in all WB measures, with the exception of AD females, which showed no significant changes in WB |G*|, G , or G .

CONCLUSION

Aging had region-specific effects on cerebral viscoelasticity, namely, WB softening and hippocampal stiffening. Amyloid plaque deposition may have sex-specific effects, which require further scrutiny.

摘要

背景与目的

阿尔茨海默病(AD)患者大脑的生物力学变化尚未完全阐明。本研究旨在探讨β-淀粉样蛋白(Aβ)聚集对小鼠脑粘弹性的影响。

方法

采用磁共振弹性成像技术计算全脑实质(WB)和双侧海马的粘弹性模量(|G*|)、弹性(G )和粘性(G )的大小,共纳入 9 只转 AD 基因 J20 (AD)小鼠(5 雄/4 雌)和 10 只野生型(WT)C57BL/6 小鼠(5 雄/5 雌),分别于 11 和 14 月龄进行检测。

结果

横断面上,两组在两个时间点均无显著差异。11 月龄时未观察到性别特异性差异,但 14 月龄时 AD 雌鼠的海马 |G*|、G 和 WB |G*|、G 、G 明显高于 AD 和 WT 雄鼠。在 AD 雌鼠和 WT 雌鼠之间也发现了类似的趋势差异,但未达到统计学意义。纵向分析显示,AD 和 WT 小鼠在 11 至 14 月龄之间,海马的 |G*|、G 、G 和 WB 的 |G*|、G 、G 均显著增加,而 WB 的 |G*|、G 、G 则显著降低。每个亚组的所有海马指标均显著增加,所有 WB 指标均显著降低,但 AD 雌鼠除外,其 WB 的 |G*|、G 或 G 无显著变化。

结论

老化对大脑粘弹性具有区域特异性影响,即 WB 软化和海马硬化。淀粉样斑块沉积可能具有性别特异性影响,需要进一步研究。

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