Adenovirus-mediated gene transfer of dopamine D-2 receptor cDNA into rat striatum

A robust feature of mammalian aging associated with diminished motor control is the loss of dopamine D-2 receptors from the neostriatum. Decline in this neurotransmitter receptor is also observed in neurodegenerative disorders, such as Huntington's disease and late-stage Parkinson's disease. We have constructed a replication-deficient adenoviral vector to transfer rat dopamine D-2 receptor cDNA to brain as a possible therapeutic strategy. Using tissue culture cells infected with this vector, we detected dopamine D-2 receptor mRNA by Northern analysis and functional receptor protein in membrane preparations as specific binding of the dopamine D-2 receptor ligand, [H-3]spiperone. In vivo demonstration involved autoradiographic analysis of [H-3]spiperone binding in rat striatum following injection of the adenoviral vector. Dopamine D-2 receptor expression was amplified markedly above normal concentrations in the injection site, whereas no increased expression was observed in sites receiving control treatments. These results demonstrate the potential of gene therapy using adenoviral vectors to transfer neurotransmitter receptor proteins to the brain to reverse deficiencies in specific neurodegenerative disorders.