Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon 21999, Republic of Korea.
Int J Mol Sci. 2023 Mar 7;24(6):5073. doi: 10.3390/ijms24065073.
This study aimed to investigate morphological and metabolic changes in the brains of 5xFAD mice. Structural magnetic resonance imaging (MRI) and H magnetic resonance spectroscopy (MRS) were obtained in 10- and 14-month-old 5xFAD and wild-type (WT) mice, while P MRS scans were acquired in 11-month-old mice. Significantly reduced gray matter (GM) was identified by voxel-based morphometry (VBM) in the thalamus, hypothalamus, and periaqueductal gray areas of 5xFAD mice compared to WT mice. Significant reductions in N-acetyl aspartate and elevation of myo-Inositol were revealed by the quantification of MRS in the hippocampus of 5xFAD mice, compared to WT. A significant reduction in NeuN-positive cells and elevation of Iba1- and GFAP-positive cells supported this observation. The reduction in phosphomonoester and elevation of phosphodiester was observed in 11-month-old 5xFAD mice, which might imply a sign of disruption in the membrane synthesis. Commonly reported H MRS features were replicated in the hippocampus of 14-month-old 5xFAD mice, and a sign of disruption in the membrane synthesis and elevation of breakdown were revealed in the whole brain of 5xFAD mice by P MRS. GM volume reduction was identified in the thalamus, hypothalamus, and periaqueductal gray areas of 5xFAD mice.
本研究旨在探讨 5xFAD 小鼠大脑的形态和代谢变化。对 10 月龄和 14 月龄的 5xFAD 和野生型（WT）小鼠进行结构磁共振成像（MRI）和 H 磁共振波谱（MRS）检查，而在 11 月龄的小鼠中进行 P MRS 扫描。与 WT 小鼠相比，基于体素的形态学（VBM）分析显示，5xFAD 小鼠的丘脑、下丘脑和导水管周围灰质区域的灰质（GM）体积明显减少。MRS 定量分析显示，与 WT 小鼠相比，5xFAD 小鼠的海马区 N-乙酰天冬氨酸减少，肌醇升高。免疫组化显示，5xFAD 小鼠的 NeuN 阳性细胞减少，Iba1 和 GFAP 阳性细胞增多，支持了这一观察结果。在 11 月龄的 5xFAD 小鼠中观察到磷酸单酯减少和磷酸二酯升高，这可能表明细胞膜合成受到干扰。在 14 月龄的 5xFAD 小鼠的海马区中复制了常见的 H MRS 特征，通过 P MRS 显示，5xFAD 小鼠的整个大脑中存在细胞膜合成中断和分解产物升高的迹象。5xFAD 小鼠的丘脑、下丘脑和导水管周围灰质区域的 GM 体积减少。
