title: Modulation of Postnatal Neurogenesis by Perinatal Asphyxia: Effect of D1and D2Dopamine Receptor Agonists.
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 D1agonist), quinpirole (10 µM, a D2agonist) or sulpiride (10 μM, a D2antagonist) + 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 D2receptors.
authors.affiliation: Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Av. Independencia 1027, PO Box 8389100, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Tapia-Bustos
authors.affiliation: Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Av. Independencia 1027, PO Box 8389100, Santiago, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Perez-Lobos
authors.affiliation: Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Av. Independencia 1027, PO Box 8389100, Santiago, Chile.
authors.forename: V
authors.initials: V
authors.lastname: Vío
authors.affiliation: Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Av. Independencia 1027, PO Box 8389100, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Lespay-Rebolledo
authors.affiliation: Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Av. Independencia 1027, PO Box 8389100, Santiago, Chile.
authors.forename: E
authors.initials: E
authors.lastname: Palacios
authors.affiliation: Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Av. Independencia 1027, PO Box 8389100, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Chiti-Morales
authors.affiliation: Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Av. Independencia 1027, PO Box 8389100, Santiago, Chile.
authors.forename: D
authors.initials: D
authors.lastname: Bustamante
authors.affiliation: Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Av. Independencia 1027, PO Box 8389100, Santiago, Chile.|Biomedical Neuroscience Institute, BNI, ICBM, Medical Faculty, University of Chile, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Herrera-Marschitz
authors.affiliation: Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Av. Independencia 1027, PO Box 8389100, Santiago, Chile. pmorales@med.uchile.cl.|Biomedical Neuroscience Institute, BNI, ICBM, Medical Faculty, University of Chile, Santiago, Chile. pmorales@med.uchile.cl.
authors.forename: P
authors.initials: P
authors.lastname: Morales
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology; D046509:Tissue Culture Techniques
chemical_list: C000607792:DRD2 protein, rat; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride
keywords: Dopamine receptor; Hippocampus; Neonatal hypoxia; Neurogenesis; Rat; Subventricular zone