Transplantation of Neuronal Precursors Derived from Induced Pluripotent Stem Cells into the Striatum of Rats with the Toxin-induced Model of Huntington's Disease

摘要

AbstractIntroduction. Huntington’s disease (HD) is a severe neurodegenerative disorder characterized by choreic hyperkinesis, cognitive decline, behavioral disorders, and progressive neuronal death, mostly in the striatum. Since HD is a fatal disorder, searching for efficient treatment methods, including those based on cell replacement therapy, is quite relevant. The experimental models of HD are used increasingly often.The objectiveof the study was to assess effectiveness and safety of transplantation of neuronal precursors differentiated from induced pluripotent stem cells (iPSCs) from a healthy donor into the striatum of rats with 3-NPAinduced HD model.Materials and methods. We studied the influence of neurotransplantation on the behavioral effects in rats with HD model induced by intrastriatal injection of 3-nitropropiotic acid (3-NPA). In the study group of animals (n= 11), human neuronal precursors derived from iPSCs of a healthy volunteer were transplanted into the caudate nuclei (5 × 105per 5 μL of normal saline solution bilaterally); the control group of animals (n= 10) received normal saline solution. The animals were tested using the ANY-maze video tracking system; the parameters of the open-field test and the conditioned avoidance response test were evaluated.Results. An analysis of behavioral effects after transplantation demonstrated that introduction of neuronal iPSC derivatives into the caudate nuclei of rats with induced HD model was accompanied by recovery of locomotor activity of the animals (horizontal and vertical), as opposed to the control group. It was found when testing the reproducibility of the conditioned avoidance responses that the conditioned avoidance responses in control animals were weakened, whereas intrastriatal transplantation of neurons abruptly increased the latency of moving into the dark compartment of the chamber in the conditioned avoidance response test.Conclusions. The pilot experiment using the HD model showed that neurotransplantation using iPSC derivatives recovers the reduced locomotor activity in rats and improves memory trace keeping, which contributes to correction of locomotor and cognitive disorders induced by 3-NPA neurotoxin.