Changes of α-Synuclein Localization in a Neuronal Precursor Graft in the Rat Model of 6-OHDA-Induced Parkinsonism.

In the experiment with transplantation of neuronal mesencephalic precursors derived from induced pluripotent stem cells into the striatum of rats with unilateral 6-OHDA destruction of the substantia nigra, we evaluated changes in the immunostaining for α-synuclein during differentiation and maturation of grafted neurons 1, 3, and 6 months after the surgery. The content of α-synuclein in transplanted neurons peaked by the third month after surgery, as well as changes in the nuclear-cytoplasmic ratio of α-synuclein in neurons by the 3rd and 6th months relative to the 1st month after transplantation were revealed. Changes in α-synuclein localization and content were associated with a gradual decrease in doublecortin expression and an increase in immunostaining for neuronal enolase and synaptophysin as the graft matured. The high content of total α-synuclein in developing neurons may be a key factor of spreading of α-synuclein toxic species in graft cells and a cause of cell damage.