Dopamine neurons heterozygous for the Nurr1-null allele have reduced survival in vitro

Although Nurr1 is essential for the differentiation of midbrain dopamine neurons, its function in mature dopamine neurons has not been determined. In order to investigate the role of Nurr1 in the survival of dopamine neurons, neurons from the mesencephalon of newborn pups heterozygous for the Nurr1-null mutation (+/-) or wild-type (+/+) littermates were grown in culture. Postnatal cultures revealed a significant reduction in the survival and growth of tyrosine hydroxylase immunoreactive (TH-IR) neurons from Nurr1 +/- pups as early as 1 day in culture despite having normal TH-IR neuron numbers in vivo. The Nurr1 +/+ and +/- TH-IR neurons responded to treatment with forskolin, glia cell-line derived neurotrophic factor and brain-derived neurotrophic factor, although significantly fewer Nurr1 +/- TH-IR neurons survived. These data suggest that the loss of a single allele of Nurr1 significantly reduces the survival capacity of postnatal dopamine neurons in vitro without affecting normal development or differentiation.