The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, BT9 7BL Belfast, Northern Ireland, United Kingdom.
Institute of Inflammation and Ageing, University of Birmingham, B15 2TT Birmingham, United Kingdom.
Proc Natl Acad Sci U S A. 2020 Jul 28;117(30):18018-18028. doi: 10.1073/pnas.1922089117. Epub 2020 Jul 10.
CCN3 is a matricellular protein that promotes oligodendrocyte progenitor cell differentiation and myelination in vitro and ex vivo. CCN3 is therefore a candidate of interest in central nervous system (CNS) myelination and remyelination, and we sought to investigate the expression and role of CCN3 during these processes. We found CCN3 to be expressed predominantly by neurons in distinct areas of the CNS, primarily the cerebral cortex, hippocampus, amygdala, suprachiasmatic nuclei, anterior olfactory nuclei, and spinal cord gray matter. CCN3 was transiently up-regulated following demyelination in the brain of cuprizone-fed mice and spinal cord lesions of mice injected with lysolecithin. However, CCN3 mice did not exhibit significantly different numbers of oligodendroglia or differentiated oligodendrocytes in the healthy or remyelinating CNS, compared to WT controls. These results suggest that despite robust and dynamic expression in the CNS, CCN3 is not required for efficient myelination or remyelination in the murine CNS in vivo.
CCN3 是一种基质细胞蛋白,可促进体外和离体少突胶质前体细胞的分化和髓鞘形成。因此,CCN3 是中枢神经系统(CNS)髓鞘形成和再髓鞘化的候选物,我们试图研究 CCN3 在这些过程中的表达和作用。我们发现 CCN3 主要由中枢神经系统不同区域的神经元表达,主要是大脑皮层、海马体、杏仁核、视交叉上核、前嗅核和脊髓灰质。在杯状藻胶喂养的小鼠大脑脱髓鞘和注射溶血磷脂酰胆碱的小鼠脊髓损伤后,CCN3 短暂上调。然而,与 WT 对照组相比,CCN3 小鼠在健康或再髓鞘化的中枢神经系统中,少突胶质细胞或分化的少突胶质细胞数量没有明显差异。这些结果表明,尽管 CCN3 在中枢神经系统中表达丰富且具有动态性,但在体内,CCN3 对于小鼠中枢神经系统的有效髓鞘形成或再髓鞘化并非必需。