| Summary: | <p>Abstract</p> <p>Background</p> <p>Parkinson’s disease is characterized by a continuous loss of neurons within the substantia nigra (SN) leading to a depletion of dopamine. Within the adult SN as a non-neurogenic region, cells with mainly oligodendrocytic precursor characteristics, expressing the neuro-glial antigen-2 (NG2) are continuously generated. Proliferation of these cells is altered in animal models of Parkinson’s disease (PD). Exercise and environmental enrichment re-increase proliferation of NG2<sup>+</sup> cells in PD models, however, a possible mechanistic role of dopamine for this increase is not completely understood. NG2<sup>+</sup> cells can differentiate into oligodendrocytes but also into microglia and neurons as observed <it>in vitro</it> suggesting a possible hint for endogenous regenerative capacity of the SN. We investigated the role of dopamine in NG2-generation and differentiation in the adult SN stimulated by physical activity and environmental enrichment.</p> <p>Results</p> <p>We used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-model for dopamine depletion and analysed newborn cells in the SN at different maturation stages and time points depending on voluntary physical activity, enriched environment and levodopa-treatment. We describe an activity- induced increase of new NG2-positive cells and also mature oligodendrocytes in the SN of healthy mice. Running and enriched environment refused to stimulate NG2-generation and oligodendrogenesis in MPTP-mice, an effect which could be reversed by pharmacological levodopa-induced rescue.</p> <p>Conclusion</p> <p>We suggest dopamine being a key regulator for activity-induced generation of NG2-cells and oliogodendrocytes in the SN as a potentially relevant mechanism in endogenous nigral cellular plasticity.</p>
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