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Motor Behavior in an MPTP Mice Model of Parkinson’s Disease Treated with Recombinant Spidroin rS1/9 Microgel

  • I. N. Rybolovlev,
  • M. M. Rudenok,
  • E. I. Semenova,
  • M. V. Shulskaya,
  • S. A. Partevian,
  • M. V. Lukashevich,
  • L. I. Davydova,
  • M. A. Klinskaya,
  • V. G. Bogush,
  • E. L. Arsenyeva,
  • L. V. Novosadova,
  • E. V. Novosadova,
  • M. I. Shadrina,
  • P. A. Slominsky

摘要

It was shown earlier that induced pluripotent stem cells (iPSCs) differentiate into a heterogeneous cell population enriched in dopaminergic neurons on a microgel matrix based on recombinant spidroin rS1/9. To further study the functional activity of the resulting neuronal culture, it was administered to mice with a toxic model of Parkinson’s disease (PD) to assess the possibility of modulating motor behavior impaired by the introduction of MPTP. Mice with a toxic model of early symptomatic PD were used for stereotaxic transplantation of neuronal cells. Motor behavior was assessed using the Open Field test. It was shown that in vitro cultivation of neuronal cells on a microgel-free medium has a pronounced effect on the motor activity of mice two weeks after their administration into the mouse’ brain and three weeks after toxic damage to neurons of the substantia nigra. The effect of short-term 3-day cultivation turned out to be negative: the motor activity of mice decreased. On the contrary, it increases with longer cultivation, which is expressed primarily in an increased duration of the active period and the distance traveled. This is especially clearly pronounced when we compare the motor activity of mice that were injected with neuronal cells cultured on a microgel-free medium for two weeks or three days. These effects are modulated by cell cultivation on a microgel, and this effect differs for neuronal cultures with different periods of in vitro cultivation. Neuronal cell cultures derived from iPSCs and differentiated in vitro can increase motor activity when they are stereotaxically introduced into the brain of mice with a toxic model of PD. This effect depends on the duration of the in vitro cell culture cultivation and on the matrices used in the cultivation process.