Striatal transplantation in a rodent model of multiple system atrophy: effects on L-Dopa response

Abstract

Progressive degeneration of striatal projection neurons is thought to account for the loss of L-Dopa response observed in the majority of patients with the parkinsonian variant of multiple system atrophy (MSA-P). Here we have investigated the effects of E14 embryonic striatal allografts on dopaminergic responsiveness in the unilateral double-lesion rat model of MSA-P by using tests of complex motor behavior. Both sham and graft animals showed an increase in apomorphine-induced rotations as well as an improvement in cylinder test performance following surgical intervention. In contrast, L-Dopa responsiveness of stepping behavior was improved only in grafted animals. The restoration of apomorphine-induced rotation correlated with the P-zone volume of grafts. Our findings indicate that transplantation of embryonic striatal grafts might, at least to some extent, restore responsiveness to L-Dopa in tasks of complex motor behavior. Therefore, striatal transplantation should be further defined preclinically as a possible therapeutic option for patients with MSA-P and a failing L-Dopa response.