Electrophysiological Properties of Adult Zebrafish Oligodendrocyte Progenitor Cells

Abstract

Low remyelination efficiency after spinal cord injury (SCI) is a major restraint to successful axonal and functional regeneration in mammals. In contrast, adult zebrafish can: (i) regenerate oligodendrocytes and myelin sheaths within 2 weeks post lesion; (ii) re-grow axonal projections across the lesion site and (iii) recover locomotor function within 6 weeks after spinal cord transection. However, little is known about the intrinsic properties of oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the central nervous system (CNS). Here, we demonstrate that purified OPCs from the adult zebrafish spinal cord are electrically active. They functionally express voltage-gated K + and Na + channels, glutamate receptors and exhibit depolarizing, tetrodotoxin (TTX)-sensitive spikes, as previously seen in rodent and human OPCs. Furthermore, we show that the percentage of zebrafish OPCs exhibiting depolarizing spikes and Na v -mediated currents is lower as compared to rodent white matter OPCs, where these membrane characteristics have been shown to underlie OPC injury susceptibility. These findings imply that adult zebrafish OPCs resemble electrical properties found in mammals and represent a relevant cell type towards understanding the biology of the primary cells targeted in remyelination therapies for non-regenerative species. The in vitro platform introduced in this study could be used in the future to: (i) elucidate how membrane characteristics of zebrafish OPCs change upon injury and (ii) identify potential signaling components underlying OPC injury recognition.

Neuron to Oligodendrocyte Precursor Cell Synapses: Protagonists in Oligodendrocyte Development and Myelination, and Targets for Therapeutics

“…OPCs show no response to depolarization in the first wave of OPC proliferation in embryonic development in the forebrain, with responses not observed in OPCs until P5 ( Ziskin et al, 2007 ), although there are responses to depolarization in the spinal cord, see Osterstock et al (2018) . However, exposure to glutamate induces mEPSCs in OPCs both in very early postnatal development and into maturity in the forebrain and spinal cord, ( De Biase et al, 2010 ; Spitzer et al, 2019 ; Tsata et al, 2019 ), and in both gray ( Bergles and Jahr, 2000 ; Mangin et al, 2008 ), and white matter ( Kukley et al, 2007 ; Ziskin et al, 2007 ; Káradóttir et al, 2008 ; Etxeberria et al, 2010 ). The degree of response to glutamate differs greatly between OPCs, pre-OLs, and OLs.…”

“…For example, adult zebrafish, unlike mammals, are capable of regenerating OLs and remyelinate axons within 2 weeks of lesion. This indicates that zebrafish glia could be a useful model for mammalian remyelination after injury or disease ( Tsata et al, 2019 ). The basic channel properties and expression in zebrafish OPCs were similar to mammalian OPCS, which opens up the possibility that determining how OPCs differently respond in this model could aid our understanding of remyelination in mammals.…”

Single cell sequencing of radial glia progeny reveals the diversity of newborn neurons in the adult zebrafish brain

“…3C) supports their generation from RG in the adult zebrafish brain. In addition, flow cytometry of double transgenic fish that combine the RG-specific her4.1:mCherry reporter with the OPC-specific reporter olig2:gfp (Shin et al, 2003;Kroehne et al, 2017;Tsata et al, 2019) [Tg(her4.1:mcherry; olig2:gfp)] revealed that 28.6±3.9% of all olig2:GFP cells were mCherry low /GFP high double positive ( Fig. S4B,C).…”

Met is required for oligodendrocyte progenitor cell migration inDanio rerio

“…Beyond developmental tiling, OPCs remain evenly tiled throughout life and utilize similar processes of migration, proliferation, contact-mediated repulsion, and apoptosis to maintain their spacing ( Hughes et al 2013 ; Tsata et al 2019 ). While a number of chemotactic molecules have been investigated in developmental OPC tiling, adult tiling and how it is maintained remains largely unknown.…”