Abstract

Neural stem cells (aNSC) are presently employed by many researchers as a restorative therapy for neurodegenerative diseases, including PD. The subventricular zone (SVZ) contains NSCs capable of giving rise to new neurons in adult mammalian brains. MPTP-induced degeneration of dopaminergic SNpc-SVZ fibres impairs NSC proliferation in primates and in mice. This study shows the DA-induced increase in NSC viability in vitro. L-DOPA and DA, being catechol-containing compounds, may undergo autoxidation in vivo in the striatal extracellular compartment, with the consequent generation of quinone derivatives. The results from this study demonstrate the inhibitory effects on NSC viability in vitro induced by Mn alone or in association with L-DOPA and the antagonism exerted by ascorbic acid (AA) . Furthermore, we demonstrated the inhibitory effects of MPTP and MPP+ on NSC viability in vitro and the complete recovery of viability exerted by DA+L-DOPA+AA. DA, L- DOPA and AA are physiological components of the striatal extracellular compartment. Therefore, the striatal levels of DA and AA, coupled with administration of exogenous L-DOPA, might help NSCs in their restorative effort in the MPTP model of PD. The main finding of this study is that aNSC possess SVCT2 which allows the cell to accumulate AA. Moreover, aNSC are able to induce the DHAA reduction back to AA. The later data consistent with the ability of stem cells to protect DA and L-DOPA from autoxidation.

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