Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination

Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination
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DOI:
10.1073/pnas.1922089117
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发表时间:
2020-07-28
影响因子:
11.1
通讯作者:
Fitzgerald, Denise C.
Fitzgerald, Denise C.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gallardo, Nira de la Vega;Penalva, Rosana;Fitzgerald, Denise C.

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CCN 3是在体外和离体促进少突胶质细胞祖细胞分化和髓鞘形成的基质细胞蛋白。因此,CCN 3是中枢神经系统(CNS)髓鞘形成和髓鞘再生中感兴趣的候选者,并且我们试图研究CCN 3在这些过程中的表达和作用。我们发现CCN 3主要由CNS不同区域的神经元表达,主要是大脑皮质、海马、杏仁核、视交叉上核、前嗅核和脊髓灰质。CCN 3在铜唑酮喂养的小鼠的脑中脱髓鞘和用溶血素注射的小鼠的脊髓损伤后瞬时上调。然而,与WT对照相比,CCN 3(-/-)小鼠在健康或髓鞘再生CNS中没有表现出显著不同数量的少突胶质细胞或分化的少突胶质细胞。这些结果表明,尽管CCN 3在CNS中有稳健和动态的表达,但CCN 3不是体内鼠CNS中有效髓鞘形成或髓鞘再形成所需的。
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.