Microcephaly with altered cortical layering in GIT1 deficiency revealed by quantitative neuroimaging.
Microcephaly with altered cortical layering in GIT1 deficiency revealed by quantitative neuroimaging.
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定量神经影像学显示GIT1缺乏症的小头畸形伴皮层分层改变。
DOI：
10.1016/j.mri.2020.09.023
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发表时间：
2021-03
影响因子：
2.5
通讯作者：
Premont RT
中科院分区：
文献类型：
--
作者：
Badea A;Schmalzigaug R;Kim W;Bonner P;Ahmed U;Johnson GA;Cofer G;Foster M;Anderson RJ;Badea C;Premont RT
G蛋白偶联受体激酶相互作用蛋白-1（GIT 1）调节神经元功能，包括细胞和轴突迁移以及突触形成和维持，GIT 1敲除（KO）小鼠表现出学习和记忆缺陷。我们注意到，雄性和雌性GIT 1-KO小鼠表现出神经成像表型，包括小头畸形和改变的皮质分层，皮质层V中的神经元密度降低。使用Micro-CT和磁共振显微镜（MRM）来识别颅骨和整个GIT 1-KO大脑的形态测定表型。来自GIT 1-KO和野生型（WT）对照的活性染色小鼠脑的高场MRM（每组n=6）允许基于与Waxholm Space图谱的共配准分割37个区域。GIT 1-KO小鼠的总体脑大小比WT对照小约32%。在校正脑大小后，GIT 1-KO小鼠中的几个区域相对于WT显著不同，包括丘脑腹侧核和丘脑其余部分的灰质、下丘和脑桥核。GIT 1-KO小鼠的白色束体积减少，最明显的是前连合（小约26%），但也存在于大脑脚、穹窿和三叉神经脊束中。另一方面，GIT 1-KO小鼠的基底神经节似乎扩大，包括苍白球、尾壳核，特别是丘脑-支持可能的成瘾易感性。基于高分辨率MRM（21.5 μm各向同性体素）的基于体积的形态测定法可有效检测GIT 1-KO小鼠脑体积的整体和局部差异，包括白色物质束。特定大脑区域的相对体积减少表明GIT 1在大脑发育中起着关键但不一致的作用，有助于大脑小头畸形和异常连接。
G Protein-Coupled Receptor Kinase-Interacting Protein-1 (GIT1) regulates neuronal functions, including cell and axon migration and synapse formation and maintenance, and GIT1 knockout (KO) mice exhibit learning and memory deficits. We noted that male and female GIT1-KO mice exhibit neuroimaging phenotypes including microcephaly, and altered cortical layering, with a decrease in neuron density in cortical layer V. Micro-CT and magnetic resonance microscopy (MRM) were used to identify morphometric phenotypes for the skulls and throughout the GIT1-KO brains. High field MRM of actively-stained mouse brains from GIT1-KO and wild type (WT) controls (n=6 per group) allowed segmenting 37 regions, based on co-registration to the Waxholm Space atlas. Overall brain size in GIT1-KO mice was ~32 % smaller compared to WT controls. After correcting for brain size, several regions were significantly different in GIT1-KO mice relative to WT, including the gray matter of the ventral thalamic nuclei and the rest of the thalamus, the inferior colliculus, and pontine nuclei. GIT1-KO mice had reduced volume of white matter tracts, most notably in the anterior commissure (~26% smaller), but also in the cerebral peduncle, fornix, and spinal trigeminal tract. On the other hand, the basal ganglia appeared enlarged in GIT1-KO mice, including the globus pallidus, caudate putamen, and particularly the accumbens - supporting a possible vulnerability to addiction. Volume based morphometry based on high-resolution MRM (21.5 μm isotropic voxels) was effective in detecting overall, and local differences in brain volumes in GIT1-KO mice, including in white matter tracts. The reduced relative volume of specific brain regions suggests a critical, but not uniform, role for GIT1 in brain development, conducive to brain microcephaly, and aberrant connectivity.
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影响因子：
5.7
作者：
Badea, Alexandra;Gewalt, Sally;Avants, Brian B.;Cook, James J.;Johnson, G. Allan
通讯作者：
Johnson, G. Allan
影响因子：
5.7
作者：
Badea A;Kane L;Anderson RJ;Qi Y;Foster M;Cofer GP;Medvitz N;Buckley AF;Badea AK;Wetsel WC;Colton CA
通讯作者：
Colton CA
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
DOI：
10.1523/jneurosci.3554-12.2013
发表时间：
2013-02-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Alexander-Bloch A;Raznahan A;Bullmore E;Giedd J
通讯作者：
Giedd J
影响因子：
3.5
作者：
Celestine, Marina;Nadkarni, Nachiket A.;Dhenain, Marc
通讯作者：
Dhenain, Marc