AUTHOR=Markert Franz , Storch Alexander TITLE=Hyperoxygenation During Mid-Neurogenesis Accelerates Cortical Development in the Fetal Mouse Brain JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.732682 DOI=10.3389/fcell.2022.732682 ISSN=2296-634X ABSTRACT=

Oxygen tension is well-known to affect cortical development. Fetal brain hyperoxygenation during mid-neurogenesis in mice (embryonic stage E14.5. to E16.5) increases brain size evoked through an increase of neuroprecursor cells. Nevertheless, it is unknown whether these effects can lead to persistent morphological changes within the highly orchestrated brain development. To shed light on this, we used our model of controlled fetal brain hyperoxygenation in time-pregnant C57BL/6J mice housed in a chamber with 75% atmospheric oxygen from E14.5 to E16.5 and analyzed the brains from E14.5, E16.5, P0.5, and P3.5 mouse embryos and pups via immunofluorescence staining. Mid-neurogenesis hyperoxygenation led to an acceleration of cortical development by temporal expansion of the cortical plate with increased NeuN+ neuron counts in hyperoxic brains only until birth. More specifically, the number of Ctip2+ cortical layer 5 (L5) neurons was increased at E16.5 and at birth in hyperoxic brains but normalized in the early postnatal stage (P3.5). The absence of cleaved caspase 3 within the extended Ctip2+ L5 cell population largely excluded apoptosis as a major compensatory mechanism. Timed BrdU/EdU analyses likewise rule out a feedback mechanism. The normalization was, on the contrary, accompanied by an increase of active microglia within L5 targeting Ctip2+ neurons without any signs of apoptosis. Together, hyperoxygenation during mid-neurogenesis phase of fetal brain development provoked a specific transient overshoot of cortical L5 neurons leading to an accelerated cortical development without detectable persistent changes. These observations provide insight into cortical and L5 brain development.