Changes in cytoskeletal gene expression linked to MPTP-treatment in Mice

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and a marked reduction of dopamine (DA) levels in the striatum. Binding to its specific receptors, DA switches on a complex program of intracellular signaling that regulates gene expression. We evaluated the changes in striatal gene expression in a mouse model of Parkinson's disease, using differential display analysis. The mRNA for the cytoskeleton family proteins, radixin, cofilin and centractin/ARP-1, was abnormally expressed in the striatum of these MPTP-treated mice. Moreover, we also found that radixin mRNA and its protein levels are under DA control through specific D1-dopaminergic receptors in a dose- and time-dependent manner in the GT1-7 neural cell line. These findings suggest a role for DA for regulation of cytoskeletal proteins involved in the integrity and function of synapsis.