Behavioural Effect of Engineered Cells that Synthesize l-dopa or Dopamine after Grafting into the Rat Neostriatum

Cell lines in which tyrosine hydroxylase was introduced either by infection or transfection were used in grafting experiments in a rat model of Parkinson's disease obtained by unilateral lesion of the substantia nigra. A neuroblastoma NS20 Y cell line which synthesizes only l-dopa and a neuroendocrine AtT-20 cell line which produces dopamine were obtained. They were grafted into denervated striata and their ability to compensate for the dopaminergic deficit was studied. Both modified cell types displayed a rapid partial reversal of apomorphine-induced turning behaviour. No effect was observed with the control unmodified cell lines. We discuss the usefulness of engineered cell lines to address the fundamental issues in grafting experiments and more particularly in the therapy of Parkinson's disease.