Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium.
Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium ; F. Hoffmann-La Roche Pharmaceuticals Ltd, Neuroscience Discovery, Basel, Switzerland.
PLoS One. 2013 Dec 17;8(12):e84241. doi: 10.1371/journal.pone.0084241. eCollection 2013.
Functional connectivity (FC) studies have gained immense popularity in the evaluation of several neurological disorders, such as Alzheimer's disease (AD). AD is a complex disorder, characterised by several pathological features. The problem with FC studies in patients is that it is not straightforward to focus on a specific aspect of pathology. In the current study, resting state functional magnetic resonance imaging (rsfMRI) is applied in a mouse model of amyloidosis to assess the effects of amyloid pathology on FC in the mouse brain.
Nine APP/PS1 transgenic and nine wild-type mice (average age 18.9 months) were imaged on a 7T MRI system. The mice were anesthetized with medetomidine and rsfMRI data were acquired using a gradient echo EPI sequence. The data were analysed using a whole brain seed correlation analysis and interhemispheric FC was evaluated using a pairwise seed analysis. Qualitative histological analyses were performed to assess amyloid pathology, inflammation and synaptic deficits.
The whole brain seed analysis revealed an overall decrease in FC in the brains of transgenic mice compared to wild-type mice. The results showed that interhemispheric FC was relatively preserved in the motor cortex of the transgenic mice, but decreased in the somatosensory cortex and the hippocampus when compared to the wild-type mice. The pairwise seed analysis confirmed these results. Histological analyses confirmed the presence of amyloid pathology, inflammation and synaptic deficits in the transgenic mice.
In the current study, rsfMRI demonstrated decreased FC in APP/PS1 transgenic mice compared to wild-type mice in several brain regions. The APP/PS1 transgenic mice had advanced amyloid pathology across the brain, as well as inflammation and synaptic deficits surrounding the amyloid plaques. Future studies should longitudinally evaluate APP/PS1 transgenic mice and correlate the rsfMRI findings to specific stages of amyloid pathology.
功能连接（FC）研究在评估多种神经退行性疾病（如阿尔茨海默病（AD））方面已得到广泛应用。AD 是一种复杂的疾病，具有多种病理特征。在患者中进行 FC 研究的问题在于，要关注病理学的特定方面并不容易。在当前的研究中，应用静息态功能磁共振成像（rsfMRI）评估淀粉样变性的小鼠模型中淀粉样蛋白病理学对小鼠大脑 FC 的影响。
在 7T MRI 系统上对 9 只 APP/PS1 转基因和 9 只野生型小鼠进行成像。使用咪达唑仑麻醉小鼠，并使用梯度回波 EPI 序列采集 rsfMRI 数据。使用全脑种子相关分析对数据进行分析，并使用成对种子分析评估半球间 FC。进行定性组织学分析以评估淀粉样蛋白病理学、炎症和突触缺失。
全脑种子分析显示，与野生型小鼠相比，转基因小鼠大脑的 FC 整体下降。结果表明，与野生型小鼠相比，转基因小鼠运动皮层的半球间 FC 相对保留，但在躯体感觉皮层和海马中下降。成对种子分析证实了这些结果。组织学分析证实了转基因小鼠中存在淀粉样蛋白病理学、炎症和突触缺失。
在当前的研究中，与野生型小鼠相比，rsfMRI 显示 APP/PS1 转基因小鼠在多个脑区的 FC 降低。APP/PS1 转基因小鼠的大脑中存在广泛的淀粉样蛋白病理学，以及围绕淀粉样斑块的炎症和突触缺失。未来的研究应纵向评估 APP/PS1 转基因小鼠，并将 rsfMRI 发现与淀粉样蛋白病理学的特定阶段相关联。
