Jiang Hanxiao, Feng Yuxue, He Guiqiong, Liu Yuanjie, Li Xiaofeng
Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China.
Front Neuroanat. 2023 Jan 6;16:1043924. doi: 10.3389/fnana.2022.1043924. eCollection 2022.
Protein O-linked mannose β1,2--acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. A growing number of studies have shown that defects in POMGNT1 affect neuronal migration and distribution, disrupt basement membranes, and misalign Cajal-Retzius cells. Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain.
We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. We also detected the distribution profile of POMGnT1 in normal adult mouse brains by immunohistochemistry and double-immunofluorescence.
In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. In terms of cell type, POMGNT1 was predominantly expressed in neurons and was mainly enriched in glutamatergic neurons; to a lesser extent, it was expressed in glial cells. At the subcellular level, POMGNT1 was mainly co-localized with the Golgi apparatus, but expression in the endoplasmic reticulum and mitochondria could not be excluded.
The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective.
蛋白质O-连接甘露糖β1,2-N-乙酰葡糖胺基转移酶1（POMGNT1）对O-甘露糖聚糖的延长至关重要。POMGNT1突变会导致肌肉-眼-脑（MEB）疾病，其主要特征之一是大脑中的解剖结构异常。越来越多的研究表明，POMGNT1缺陷会影响神经元迁移和分布，破坏基底膜，并使Cajal-Retzius细胞排列紊乱。有几项研究已经检测了POMGNT1在胎儿或新生儿大脑中的分布和表达，用于小鼠或人类大脑的神经发育研究。然而，关于POMGNT1在正常成年小鼠大脑中的神经解剖分布和表达知之甚少。
我们通过蛋白质免疫印迹法和逆转录定量聚合酶链反应（RT-qPCR）分析了POMGNT1 mRNA和蛋白质在各种神经解剖区域的大脑和脊髓中的表达。我们还通过免疫组织化学和双重免疫荧光检测了POMGnT1在正常成年小鼠大脑中的分布情况。
在本研究中，我们发现POMGNT1阳性细胞广泛分布于大脑的各个区域，在大脑皮层和海马体中表达水平较高。就细胞类型而言，POMGNT1主要在神经元中表达，并且主要富集于谷氨酸能神经元；在较小程度上，它也在胶质细胞中表达。在亚细胞水平上，POMGNT1主要与高尔基体共定位，但不能排除在内质网和线粒体中的表达。
本研究表明，POMGNT1虽然在大脑的各个区域广泛表达，但可能具有一些区域和细胞特异性，本研究结果从形态学角度为揭示POMGNT1可能参与大脑正常生理功能提供了新的实验依据。
