Postnatal cell proliferation in the hippocampus is modulated by dopaminergic systems in the rat : effect of perinatal asphyxia

Abstract

Postnatal neurogenesis has been observed in brain regions, such as dentate gyrus of the hippocampus and subventricular zone of telencephalon. Postnatal neurogenesis is an active phenomenon modulated by several factors including monoamine transmission. Mesencephalic dopamine (DA) neurons have been observed to project to the hippocampus, although a detailed map of that projection is still lacking, and the modulation of neurogenesis by DA is still controversial. Neurocircuitries of the basal ganglia and hippocampus are vulnerable to global anoxia/ischemia occurring at the neonatal stage. We have investigated here on the DA modulation of postnatal cell proliferation and neurogenesis in hippocampus using organotypic cultures from control and asphyxia-exposed rats. Tissue from hippocampus, substantia nigra (SN) and/or ventral tegmental area (VTA) was taken at P1-3 for preparing organotypic cultures, plated on a coverslip and cultured for 22-24 days. The cultures were treated with 5-bromo-2’deoxyuridine (BrdU, 10µM), a marker of mitosis, and apomorphine (10mM), a DA agonist, for 48h. At P22-24, the cultures were fixed and treated for immunocytochemistry, using selective antibodies for tyrosine hydroxylase, microtubule-associated protein-2, and BrdU, evaluated with confocal microscopy. We found that: (i) DA neurons project to hippocampus, under in vivo and in vitro conditions. (ii) Postnatal hippocampal cell proliferation occurs under in vivo and in vitro conditions, both in control and asphyxia-exposed animals. In hippocampus monocultures cell proliferation was increased in tissue from asphyxia-exposed animals when compared to the control condition. However, cell proliferation was only increased in hippocampus/VTA control cultures. (iii) Apomorphine treatment increased cell proliferation in hippocampal monocultures from both control and asphyxia-exposed animals. This study demonstrates the modulation of postnatal neurogenesis taking place in hippocampus by DA, which is vulnerable to perinatal asphyxia.