Anatomy, Section of Medicine, University of Fribourg, Route Albert-Gockel 1, CH-1700, Fribourg, Switzerland.
Sci Rep. 2019 Jul 22;9(1):10603. doi: 10.1038/s41598-019-47112-9.
Forebrain glial cells - ependymal cells and astrocytes -acquire upon injury- a "reactive" phenotype associated with parvalbumin (PV) upregulation. Since free radicals, e.g. reactive oxygen species (ROS) play a role in the pathogenesis of multiple sclerosis, and that PV-upregulation in glial cells is inversely correlated with the level of oxidative stress, we hypothesized that PV-upregulation might also protect oligodendrocytes by decreasing ROS production. Lentiviral transduction techniques allowed for PV overexpression in CG4 oligodendrocyte progenitor cells (OPCs). Depending on the growth medium CG4 cells can be maintained in an OPC-like state, or induced to differentiate into an oligodendrocyte (OLG)-like phenotype. While increased levels of PV had no effect on cell proliferation and invasiveness in vitro, PV decreased the mitochondria volume in CG4 cell bodies, as well as the mitochondrial density in CG4 processes in both OPC-like and OLG-like states. In line with the PV-induced global decrease in mitochondrial volume, elevated PV levels reduced transcript levels of mitochondrial transcription factors involved in mitochondria biogenesis. In differentiated PV-overexpressing CG4 cells with a decreased mitochondrial volume, UV-induced ROS production was lower than in control CG4 cells hinting towards a possible role of PV in counteracting oxidative stress. Unexpectedly, PV also decreased the length of processes in undifferentiated CG4 cells and moreover diminished branching of differentiated CG4 cell processes, strongly correlated with the decreased density of mitochondria in CG4 cell processes. Thus besides conferring a protective role against oxidative stress, PV in a cell autonomous fashion additionally affects process' growth and branching in CG4 cells.
前脑神经胶质细胞——室管膜细胞和星形胶质细胞——在受伤后获得一种与副甲状腺球蛋白（PV）上调相关的“反应性”表型。由于自由基，例如活性氧（ROS），在多发性硬化症的发病机制中起作用，并且神经胶质细胞中的 PV 上调与氧化应激水平呈负相关，我们假设 PV 上调也可能通过减少 ROS 产生来保护少突胶质细胞。慢病毒转导技术允许在 CG4 少突胶质前体细胞（OPC）中过表达 PV。根据生长培养基，CG4 细胞可以保持在 OPC 样状态，或者被诱导分化为少突胶质细胞（OLG）样表型。虽然 PV 水平的增加对体外细胞增殖和侵袭性没有影响，但 PV 减少了 CG4 细胞体中的线粒体体积，以及在 OPC 样和 OLG 样状态下 CG4 突起中的线粒体密度。与 PV 诱导的线粒体体积整体减少一致，升高的 PV 水平降低了参与线粒体生物发生的线粒体转录因子的转录水平。在具有降低的线粒体体积的分化的 PV 过表达 CG4 细胞中，UV 诱导的 ROS 产生低于对照 CG4 细胞，暗示 PV 可能在对抗氧化应激中起作用。出乎意料的是，PV 还减少了未分化 CG4 细胞中突起的长度，并且减少了分化的 CG4 细胞突起的分支，与 CG4 细胞突起中线粒体密度的降低强烈相关。因此，除了赋予对抗氧化应激的保护作用外，PV 还以细胞自主的方式另外影响 CG4 细胞中突起的生长和分支。
