In vivo MRI reveals the dynamics of pathological changes in the brains of cathepsin D-deficient mice and correlates changes in manganese-enhanced MRI with microglial activation lift
In vivo MRI reveals the dynamics of pathological changes in the brains of cathepsin D-deficient mice and correlates changes in manganese-enhanced MRI with microglial activation lift
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DOI：
10.1016/j.mri.2007.03.012
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发表时间：
2007-09-01
影响因子：
2.5
通讯作者：
Tyynelae, Jaana
中科院分区：
文献类型：
--
作者：
Haapanen, Aleksi;Ramadan, Usama Abo;Tyynelae, Jaana
组织蛋白酶D(Cthepsin D，CTSD；EC 3.4.23.5)对于中枢神经系统神经元的正常发育和/或维持是必不可少的：它的缺失会导致人类、绵羊和小鼠严重缩短寿命的破坏性神经疾病。在神经病理学上，CTSD缺陷的特征是选择性神经元变性、胶质增生和神经元中自发荧光蛋白类储存物质的堆积。我们的目的是通过活体磁共振成像(MRI)和组织学的方法，研究CTSD缺陷(CTSD-/-)小鼠脑内发生病理变化的动力学。为此，我们测量了疾病进展过程中三个时间点的磁共振图像的T-2信号强度(SI)、表观扩散系数、面积和体积。核磁共振显示CTSD-/-小鼠和对照组小鼠在出生后15+/-1天(P15+/-1)的大脑没有差异，代表了疾病的初始阶段。在疾病的中期，P19(+/-1)，在T-1和T-2加权图像中，受影响小鼠丘脑的SI改变变得明显。终末期P25以CTSD-/-小鼠T-2SI、表观弥散系数和多个脑结构体积明显改变为特征。此外，锰增强高分辨率T-1加权3D序列(MEMRI)和组织学染色显示，MEMRI中的高信号区域与终末期CTSD-/-小鼠大脑中的小胶质细胞激活区域完全匹配。综上所述，CTSD-/-小鼠丘脑的SI改变先于其他改变，在P19(1)龄时，变性过程大大加强，导致仅6天内脑体积严重缩小。(C)2007 Elsevier Inc.保留所有权利。
Cathepsin D (CTSD; EC 3.4.23.5) is essential for normal development and/or maintenance of neurons in the central nervous system: its deficiency causes a devastating neurological disorder with severely shortened life span in man, sheep and mouse. Neuropathologically, the CTSD deficiencies are characterized by selective neuronal degeneration, gliosis and accumulation of autofluorescent proteinaceous storage material in neurons. Our aim was to study the dynamics behind the pathological alterations occurring in the brains of CTSD-deficient (CTSD-/-) mice by using in vivo magnetic resonance imaging (MRI) and histology. In order to do this, we measured T-2 signal intensity (SI), apparent diffusion coefficient, area and volume of multiple brain structures from MR images acquired using T-2-, T-1- and diffusion-weighted sequences at three time points during disease progression. MRI revealed no differences in the brains between CTSD-/- and control mice at postnatal day 15 +/- 1 (P15 +/- 1), representing an initial stage of the disease. In the intermediate stage of the disease, P19(+/-1), SI alterations in the thalami of the affected mice became evident in both T-1- and T-2-Weighted images. The terminal stage of the disease, P25, was characterized by marked alterations in the T-2 SI, apparent diffusion coefficient and volume of multiple brain structures in CTSD-/- mice. In addition, manganese enhanced high-resolution T-1-weighted 3D sequences (MEMRI) and histological stainings revealed that the hyperintense signal areas in MEMRI matched perfectly with areas of microglial activation in the brains of CTSD-/- mice at the terminal disease stage. In conclusion, the SI alterations in the thalami of CTSD-/- mice preceded other changes, and the degenerative process was greatly enhanced at the age of P 1 9( 1), leading to severely reduced brain volume in just 6 days. (C) 2007 Elsevier Inc. All rights reserved.