Parvalbumin expression in oligodendrocyte-like CG4 cells causes a reduction in mitochondrial volume, attenuation in reactive oxygen species production and a decrease in cell processes' length and branching

Sci Rep. 2019 Jul 22;9(1):10603. doi: 10.1038/s41598-019-47112-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Mice
  • Microscopy, Confocal
  • Mitochondria / metabolism*
  • Oligodendroglia / metabolism*
  • Oligodendroglia / pathology
  • Oligodendroglia / ultrastructure
  • Parvalbumins / metabolism*
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Parvalbumins
  • Reactive Oxygen Species