gms | German Medical Science

Objective: Neural transplantation has been demonstrated to be a potential therapy for Huntington’s disease (HD). In this study, we investigated the different neuroanatomical and behavioral effects of single- (ST) and multi-tract (MT) transplants performed in an HD rodent model.

Methods: 44 Sprague-Dawley rats received unilateral quinolinic acid (QA) injections into the left striatum, with 15 rats serving as controls. Ten days post-lesion, the animals received single-cell suspension grafts prepared from the whole ganglionic eminence of E15 GFP rat embryos. The rats received either ST (1 tract/2 deposits) or MT (9 tracts/18 deposits) grafts using a 2µl Hamilton’s syringe with a glass capillary. Both groups were injected with 480,000 cells in total. Prior to lesioning and grafting, the animals were tested in terms of spontaneous tasks sensitive to lateralized deficits, as well as for skilled forelimb use. Post surgery, the animals’ performances were again evaluated in this way as well as by apomorphine-induced rotation testing at 6 days after lesion and at 4, 8, and 12 weeks following transplantation. Next, the rats were processed for immunohistochemistry. Volumetric analysis associated with the lesion and the graft was carried out with image analysis software and a light microscope.

Results: Unilateral QA lesion resulted in ipsilateral drug-induced rotation bias and functional deficits predominantly in contralateral limb and paw use. Graft-mediated behavioral improvement did not reach significance in either the skilled forelimb or the rotation tests. However, functional recovery was found in the table lift test. Immunohistochemistry revealed that the grafts were well developed in both transplantation groups, and consistently higher, but non-significant mean values were found in the MT group in terms of graft volume, DARPP-32, and TH patch volumes compared with the ST group. The work of counting DARPP-32-positive cells and further evaluation is still ongoing and will be presented at the conference.

Conclusions: The beneficial effects of multi-deposit microtransplantation seen in the rodent PD model could not be replicated in the striatal cell transplantation study using a rat HD model. Grafts in the MT group exhibited a tendency towards better cell survival, better graft development and more DARPP-32 and TH patches, which indicated that MT approach could be considered as a potential strategy which could likely produce favorable outcomes in further studies in the excitotoxic animal model of HD.