A Primate Model of Huntington’s Disease: Unilateral Striatal Lesions and Neural Grafting in the Baboon (Papio papio)

Abstract

A striking neuropathological similarity has been shown between excitatory striatal lesions in the rat and Huntington’s disease (HD). Thus, excitatory lesions in rats have served extensively as experimental models of HD (Coyle and Schwartz, 1983; Isacson et al., 1985; Beal et. al., 1986; Sanberg et al., 1989). A large body of data now supports the notion that this lesion is similar to the striatal lesion observed in HD and that this rat model can mimic the neurological dysfunction associated with the striatal degeneration in Huntingtonian patients. However, motor manifestations in lesioned rodents are restricted to changes in locomotor activity and do not include dyskinesias or chorea-like movements. The therapeutic predictions from the rodent model are therefore limited compared to data that could be obtained from other species, especially primates. In order to study the neurological basis for dyskinesias associated with striatal dysfunction in the primate and to test new therapeutic strategies for the treatment of HD such as neural transplantation, we have developed a striatal excitotoxic lesion model in primates using ibotenic acid (IA) as excitotoxin. In this study data are presented showing: 1) the occurrence in the primate of “chorea-like” movements. relevant to HD following excitotoxic lesion of the caudate nucleus and putamen. 2) the survival and the anatomical and functional characteristics of fetal rat striatal cells following their implantation into the neuron-depleted striatum of the baboon.