Behavioral and anatomical correlates of immunologically induced rejection of nigral xenografts

Abstract

Cell suspensions derived from the ventral mesencephalon of CD-1 mice were unilaterally transplanted into the striatum of neonatal Sprague-Dawley rats that had been bilaterally dopamine depleted. Thirty-eight percent of the grafts survived. Tyrosine-hydroxylase-immunoreactive neurons within the transplant innervated the host striatum with a dense fiber plexus. The grafts appeared to exert some degree of functional control over motor behavior in that these animals made contralateral rotations in response to amphetamine and tail pinch. In order to provide additional evidence that the motor behavior is associated with the transplant itself, the graft was removed. This was achieved by using a mouse skin graft to provoke an immunological response against the transplanted neural tissue. The immunological response resulted in the specific loss of the transplant with little or no damage to the surrounding neural tissue. The amount of rotation observed after tail pinch and amphetamine injection was severely affected by neural graft rejection. The loss of turning was associated most directly with the loss of tyrosine hydroxylase immunoreactivity within the transplant rather than with the massive reduction of tyrosine-hydroxylase-positive fibers in the ipsilateral host striatum. These data suggest that dopamine cells in mouse nigral grafts play an essential role in eliciting rotational behavior in neonatally dopamine depleted rats. They also show the value of skin grafting as a technique for specifically removing neural xenografts.