Abstract

Perinatal asphyxia occurs still with great incidence whenever delivery is prolonged, despite improvements of perinatal care. After asphyxia, infants can suffer from long-term neurological sequelae, their severity depending upon the extent of the insult. At present, there is not any accepted therapeutic strategy for significantly preventing the long-term effects produced by perinatal asphyxia. The present proposal is for investigating the mechanisms by which perinatal asphyxia affects and primes the development of the CNS, in particular neurocircuitries of basal ganglia and hippocampus, vulnerable to global anoxia/ischemia occurring at neonatal stages. The project assigns a pivotal role to postnatal neurogenesis, as a target for functional recovery, mainly in SVZ and DG, neurogenic regions of basal ganglia and hippocampus, respectively. The hypothesis is about dopaminergic modulation of postnatal neurogenesis, involving intracellular second messenger systems, including a newly characterised family of RGS proteins. The proposal will characterise the dopaminergic innervation of SVZ and DG, identifying the type of receptors and the metabolic cascades leading to cell proliferation occurring in those regions. The proposal implies in vivo and in vitro experiments, using histochemical, biochemical and molecular methodologies, including virus-transfection for transcription or silencing of specific genes. The proposed studies are expected to improve our understanding of the signalling pathways modulating neurogenesis, under control and hypoxic/ischemic conditions, identifying novel targets for therapeutic interventions. This proposal will provide insights on the plastic role played by postnatal neurogenesis.