Dopamine Neuron Agenesis in Nurr1-Deficient Mice

TLDR

Dopamine neurons in the substantia nigra and ventral tegmental area control movement and affective behavior and degenerate in Parkinson’s disease, and the orphan nuclear receptor Nurr1 is expressed in developing dopamine neurons before phenotypic markers appear. Nurr1 knockout mice fail to produce midbrain dopaminergic neurons, are hypoactive, and die shortly after birth, while heterozygotes show reduced dopamine levels, indicating that Nurr1 ligands could treat Parkinson’s disease and related disorders.

Abstract

Dopamine neurons of the substantia nigra and ventral tegmental area regulate movement and affective behavior and degenerate in Parkinson’s disease. The orphan nuclear receptor Nurr1 was shown to be expressed in developing dopamine neurons before the appearance of known phenotypic markers for these cells. Mice lacking Nurr1 failed to generate midbrain dopaminergic neurons, were hypoactive, and died soon after birth. Nurr1 expression continued into adulthood, and brains of heterozygous animals, otherwise apparently healthy, contained reduced dopamine levels. These results suggest that putative Nurr1 ligands may be useful for treatment of Parkinson’s disease and other disorders of midbrain dopamine circuitry.