Abstract
Hypoxia in newborns tends to result in developmental deficiencies in the white matter of the brain. As previous studies of the effects of hypoxia on neuronal development in rodents and human infants have been unable to use in vivo imaging, insight into the dynamic development of oligodendrocytes (OLs) in the central nervous system under hypoxia is limited. Here, we developed a visual model to study OL development using sublethal postnatal hypoxia in zebrafish larvae. We observed that hypoxia significantly suppressed OL progenitor cell migration toward the dorsum using in vivo imaging. Further, we found that hypoxia affected myelination, as indicated by thinner myelin sheaths and by a downregulation of myelin basic protein expression. Bmp2b protein expression was also significantly downregulated following hypoxia onset. Using gain of function and loss of function experiments, we demonstrated that the Bmp2b protein was associated with the regulation of OL development. Thus, our work provides a visual hypoxia model within which to observe OL development in vivo, and reveals the underlying mechanisms involved in these processes.
Highlights
Prior clinical research has indicated that adequate oxygen delivery is vital for brain development in infants (Hack et al, 2000; Back et al, 2006; Chahboune et al, 2009)
Using a Bmp2b receptor inhibitor and bmp2b messenger RNA rescue strategy, we demonstrated that Bmp2b participated in regulating OL development under hypoxia
Preliminary experiments showed that the gene expression of hif1α and the protein expression of Hif1α increased in response to hypoxia (Figures 1C,D)
Summary
Prior clinical research has indicated that adequate oxygen delivery is vital for brain development in infants (Hack et al, 2000; Back et al, 2006; Chahboune et al, 2009). Many investigators have modeled clinical symptoms in experimental animals by exposing neonatal rodents to different degrees and durations of hypoxia (Ganat et al, 2002; Kanaan et al, 2006; Zhou et al, 2008; Fagel et al, 2009) In both mice and rats, hypoxia reduces the volumes of the cerebral cortex and corpus callosum, and eventually leads to liberal ventriculomegaly (Weiss et al, 2004; Watzlawik et al, 2015). Hypoxia presumably abrogates the development and cognitive potential of the newborn brain (Huppi et al, 2001; Sabatino et al, 2003). Hypoxia Delays Oligodendrocyte Development neural behavior, especially OL behavior, in the spinal cord has rarely been monitored in vivo in conjunction with hypoxia
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
