Low atmospheric oxygen avoids maturation, senescence and cell death of murine mesencephalic neural precursors

AbstractThe efficient generation of specific brain cells in vitro mayserve as a source of cells for brain repair in several devas-tating neurological diseases. Production of dopaminergicneurons from precursor cells for transplantation in Parkinson’sdisease has become a major research goal. We found thatmurine mesencephalic neurospheres were viable and prolif-erated, preserved telomerase activity, pluripotency and dop-aminergic commitment for many weeks when cultured in 3%O 2 , whereas exposing these cells to 21% oxygen prohibitedlong-term expansion. Microarray data suggest that a variety ofgenes related to the cell cycle, cell maturation and apoptosisare differentially regulated in midbrain-derived precursorscultured in 3 versus 21% oxygen after 1–2 months. Takentogether, we hypothesize that sustained high oxygen hasdeleterious effects on the self-renewal capacity of mesence-phalic neural precursors, possibly accelerating maturation andsenescence resulting in overall cell loss. Gene regulationgoverned by low oxygen tension may be relevant to the nor-mal development and survival of midbrain neurons.Keywords: microarray, neural precursors, neurospheres,oxygen, proliferation, telomerase.J. Neurochem. (2005) 92, 718–729.