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PMID:27638511

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Citation

Tapia-Bustos, A, Perez-Lobos, R, Vío, V, Lespay-Rebolledo, C, Palacios, E, Chiti-Morales, A, Bustamante, D, Herrera-Marschitz, M and Morales, P (2017) Modulation of Postnatal Neurogenesis by Perinatal Asphyxia: Effect of D and D Dopamine Receptor Agonists. Neurotox Res 31:109-121

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 D agonist), quinpirole (10 µM, a D agonist) or sulpiride (10 μM, a D 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 D receptors.

Links

PubMed Online version:10.1007/s12640-016-9669-6

Keywords

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology; Animals; Animals, Newborn; Asphyxia Neonatorum/drug therapy; Asphyxia Neonatorum/metabolism; Asphyxia Neonatorum/pathology; Cell Death/drug effects; Cell Death/physiology; Cell Proliferation/drug effects; Cell Proliferation/physiology; Cell Survival/drug effects; Cell Survival/physiology; Dopamine Agonists/pharmacology; Dopamine Antagonists/pharmacology; Female; Hippocampus/drug effects; Hippocampus/metabolism; Hippocampus/pathology; Male; Neurogenesis/drug effects; Neurogenesis/physiology; Quinpirole/pharmacology; Rats, Wistar; Receptors, Dopamine D1/agonists; Receptors, Dopamine D1/metabolism; Receptors, Dopamine D2/agonists; Receptors, Dopamine D2/metabolism; Stem Cell Niche/drug effects; Stem Cell Niche/physiology; Sulpiride/pharmacology; Tissue Culture Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:DRD2

involved_in

GO:0050769: positive regulation of neurogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:DRD2

involved_in

GO:0060548: negative regulation of cell death

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:DRD1

involved_in

GO:0060548: negative regulation of cell death

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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