Cortical neurogenesis enhanced by chronic perinatal hypoxia.
Most regions of the mature mammalian brain, including the cerebral cortex, appear to be unable to support the genesis of new neurons. Here, we report that a low level of neurogenesis occurs in the cerebral cortex of the infant mouse brain and is enhanced by chronic perinatal hypoxia. When mice were reared in a low-oxygen environment from postnatal days 3 to 11, approximately 30% of the cortical neurons were lost after the insult; yet this damage was transient. The loss of cortical neuron number, cortical volume, and brain weight were all reversed during the recovery period. At P18, 7 days after the cessation of hypoxia, there was a marked increase in astroglial cell proliferation within the SVZ, as assessed by 5-bromodeoxyuridine (BrdU) incorporation in S-phase cells. One month after BrdU incorporation, 40% more BrdU-positive cells were found in the cerebral cortex of hypoxic-reared as compared to normoxic control mice. Among these newly generated cortical cells, approximately 45% were oligodendrocytes, 35% were astrocytes, and 10% were neurons in both hypoxic and normoxic mice. However, twice as many BrdU-labeled cells expressed neuronal markers in the neocortex in mice recovering from hypoxia as compared to controls. In both hypoxic-reared and normoxic infant/juvenile mice, putative neuroblasts could be seen detaching from the forebrain subventricular zone, migrating through the subcortical white matter and entering the lower cortical layers, 5 to 11 days after their last mitotic division. We suggest that cortical neurogenesis may play a significant role in repairing neuronal losses after neonatal injury.
Fagel
Devon M
DM
Child Study Center, Yale University Medical School, 230 South Frontage Road, New Haven, CT 06520, USA.
Ganat
Yosif
Y
Silbereis
John
J
Ebbitt
Timothy
T
Stewart
William
W
Zhang
Heping
H
Ment
Laura R
LR
Vaccarino
Flora M
FM
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology*; D002552:Cerebral Ventricles / Q000502:physiology; D051959:ELAV Proteins / Q000378:metabolism; D000860:Hypoxia / Q000473:pathology* / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051959:ELAV Proteins; D007211:Indoles; C007293:DAPI; D005680:gamma-Aminobutyric Acid; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine