Dopaminergic stimulation in a transgenic model of neurodegeneration restores decreased proliferation and viability in subventricular zone derived adult neural precursor cells

Protein-accumulation is one of the common neuropathological hallmarks in neurodegenerative disorders. In Parkinsonʼs disease (PD), which not only strikes by its motor deficits but also by cognitive impairment at later stages, α-Synuclein (aSyn) is accumulating and can be seen as Lewy bodies. The subventricular zone (SVZ) is the largest neurogenic region in the forebrain. Adult neural stem and precursor cells (aNSPCs) proliferate within the SVZ. Transgenic (tg) mice overexpressing human mutant A53T (hA53T) aSyn show a reduced proliferation of aNSPCs. Interestingly, in vivo studies suggest that dopaminergic treatment, which is frequently used as symptomatic treatment for PD associated motor symptoms, may have the potential to induce proliferation of aNSPCs. In vitro, a reduced number of aNSPCs and increased toxicity was observed in hA53T tg mice within the first 12 hours after seeding. In addition, 6-hydroxy dopamine (6-OHDA) induced a higher cell-toxicity related to cell loss in hA53T tg aNSPCs. Viability and proliferation of aNSPCs was significantly reduced in hA53T. Administration of dopamine was able to reverse the reduced proliferation in the hA53T model. In summary, hA53T but not hWT αSyn tg aNSPCs showed reduced proliferation and viability and were more sensitive to 6-OHDA exposure. However, dopamine was able to improve viability of aNSPCs suggesting that symptomatic treatment with dopamine has a proneurogenic effect in PD.

This study was supported by IZKF – Interdisciplinary center for clinical research, FAU Erlangen, Erlangen, Germany