Morphochemical evaluation of neurotransplantation outcomes in experimental Parkinsonism

Parkinson’s disease is characterized by degeneration of the nigrostriatal dopaminergic pathway that underlies the basic motor symptoms of the disease. Since the currently available antiparkinsonian therapy is symptomatic by its nature, approaches associated with intracerebral transplantation of functionally intact dopaminergic neurons derived from fibroblasts through the stage of induced pluripotent stem cells (iPSCs) are considered as an alternative. In this work, based on a model of 6-OHDA-induced Parkinsonism in rats, we have studied the long-term motor effects and provided morphochemical evaluation of the outcomes of human iPSC-derived dopaminergic neuron transplantation into the animal striatum. Neurotransplantation in the main group of animals (n=8) resulted in significant improvement in the motor functions and a reduction of the Parkinsonism symptoms, while similar transplantation of fibroblasts into the animal striatum in the control group (n=4) had no effect on the Parkinsonism symptoms. Immunomorphological analysis demonstrated that differentiated human neurons, which were transplanted into the rat brain, retain their localization in the striatum and remain viable for up to four months after surgery. In this case, the outgrowth of their processes around the transplantation site was observed. The study has demonstrated the fundamental possibility for movement disorders in experimental animals with a 6-OHDA-model of Parkinsonism due to the repopulation of dopaminergic neurons, the source of which may be iPSCs derived from somatic cells (fibroblasts).