Abstract
Perinatal asphyxia (PA) is associated to delayed cell death, affecting neurocircuitries of basal ganglia and hippocampus, and long-term neuropsychiatric disabilities. Several compensatory mechanisms have been suggested to take place, including cell proliferation and neurogenesis. There is evidence that PA can increase postnatal neurogenesis in hippocampus and subventricular zone (SVZ), modulated by dopamine, by still unclear mechanisms. We have studied here the effect of selective dopamine receptor agonists on cell death, cell proliferation and neurogenesis in organotypic cultures from control and asphyxia-exposed rats. Hippocampus and SVZ sampled at 1–3 postnatal days were cultured for 20–21 days. At day in vitro (DIV) 19, cultures were treated either with SKF38393 (10 and 100 µM, a D1 agonist), quinpirole (10 µM, a D2 agonist) or sulpiride (10 μM, a D2 antagonist) + quinpirole (10 μM) and BrdU (10 μM, a mitosis marker) for 24 h. At DIV 20–21, cultures were processed for immunocytochemistry for microtubule-associated protein-2 (MAP-2, a neuronal marker), and BrdU, evaluated by confocal microscopy. Some cultures were analysed for cell viability at DIV 20–21 (LIVE/DEAD kit). PA increased cell death, cell proliferation and neurogenesis in hippocampus and SVZ cultures. The increase in cell death, but not in cell proliferation, was inhibited by both SKF38393 and quinpirole treatment. Neurogenesis was increased by quinpirole, but only in hippocampus, in cultures from both asphyxia-exposed and control-animals, effect that was antagonised by sulpiride, leading to the conclusion that dopamine modulates neurogenesis in hippocampus, mainly via D2 receptors.
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Contract Grant sponsors: FONDECYT-Chile 1110263; 1120079; 1170146; 1170074; Millenium Initiative-2010 BNI (P09-015-F; Chile). ATB (#21151232), RPL (#1110263), CLR (#21140281) are CONICYT PhD Fellows; VVM is a MECESUP (UCH0714) fellow. The skillful technical support by Mr Juan Santibanez, Ms Carmen Almeyda is acknowledged.
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Tapia-Bustos, A., Perez-Lobos, R., Vío, V. et al. Modulation of Postnatal Neurogenesis by Perinatal Asphyxia: Effect of D1 and D2 Dopamine Receptor Agonists. Neurotox Res 31, 109–121 (2017). https://doi.org/10.1007/s12640-016-9669-6
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DOI: https://doi.org/10.1007/s12640-016-9669-6