2 Institute of the general genetics of N.I.Vavilov, Russian Academy of Sciences, Moscow, Russia
Dopamine deficiency in nigrostriatal system is the dominant neurotransmitter disruption causing the main clinical manifestations of Parkinson disease. Modern methods of treatment of this disease allow to reduce expressiveness of the different symptoms, however carried-out replaceable therapy doesn't prevent further progressing of neurodegenerative process. The most perspective approach in therapy of Parkinson disease is restore of dopamine deficit by applying of cellular technologies, namely transplantation of the differentiated dopaminergic neurons received from the human induced pluripotent stem cells (IPSC) into a brain of the patients.
Work was performed on Wistar male rats, at the age of 3-4 months. To obtain animal model of Parkinson disease 6-hydroxidopamine (6-OHDA) was administrated according to stereotaxic coordinates into substantia nigra of rat brain unilaterally (right side) in a dose 8 g in 4l 0,05% L-ascorbic acid/0,9% saline at a rate of 0,4 μl/min. 4 weeks after 6-OHDA administration, against the developed parkinson’s syndrome, the suspension containing of 1х106 differentiated dopaminergic neurons in 10 μl of saline was administrated according to stereotaxic coordinates into striatum of rat brain. Administration of cells was carried out ipsilaterally to neurotoxic lesion. All rats-recipients received injections of cyclosporin A (15 mg/kg) as a immunosuppressive agent daily throughout all postoperative period. After transplantation a motor activity of animals in "open field" was weekly tested.
The following results were obtained: substantial increase of motor activity and reduction of a rigidity and ptosis were observed in one week in all rats-recipients. During the next 6 weeks of observation the value of motor activity remained significantly higher compared with before surgery. The muscular rigidity, disruption of poses and ptosis completely regressed in the operated animals by the end of the 6th week of observation. There was no dyskinesia also.Thus, transplantation of functionally safe dofaminergic neurons into a brain can become real therapeutic alternative at treatment of Parkinson disease.