Morphochemical evaluation of neurotransplantation outcomes in experimental Parkinsonism

Abstract

Parkinsons disease is characterized by degeneration of the nigrostriataldopaminergic pathway that underlies the basic motorsymptoms of the disease. Since the currently available antiparkinsoniantherapy is symptomatic by its nature, approaches associatedwith intracerebral transplantation of functionally intactdopaminergic neurons derived from fibroblasts through the stageof induced pluripotent stem cells (iPSCs) are considered as analternative. In this work, based on a model of 6-OHDA-inducedParkinsonism in rats, we have studied the long-term motor effectsand provided morphochemical evaluation of the outcomesof human iPSC-derived dopaminergic neuron transplantationinto the animal striatum. Neurotransplantation in the maingroup of animals (n=8) resulted in significant improvement inthe motor functions and a reduction of the Parkinsonism symptoms,while similar transplantation of fibroblasts into the animalstriatum in the control group (n=4) had no effect on the Parkinsonismsymptoms. Immunomorphological analysis demonstratedthat differentiated human neurons, which were transplantedinto the rat brain, retain their localization in the striatum andremain viable for up to four months after surgery. In this case,the outgrowth of their processes around the transplantation sitewas observed. The study has demonstrated the fundamental possibilityfor movement disorders in experimental animals with a6-OHDA-model of Parkinsonism due to the repopulation of dopaminergicneurons, the source of which may be iPSCs derivedfrom somatic cells (fibroblasts).

Keywords

• parkinsonism
• 6-ohda
• induced pluripotent stem cells, dopaminergic neurons
• neurotransplantation
• immunomorphochemical analysis