title: Physical activity and environmental enrichment regulate the generation of neural precursors in the adult mouse substantia nigra in a dopamine-dependent manner.
abstract: BACKGROUND
  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+ cells in PD models, however, a possible mechanistic role of dopamine for this increase is not completely understood. NG2+ cells can differentiate into oligodendrocytes but also into microglia and neurons as observed in vitro 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Charité University Medicine Berlin; CCM, Charitéplatz 1, Berlin, 10117, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Klaissle
authors.forename: Anne
authors.initials: A
authors.lastname: Lesemann
authors.forename: Petra
authors.initials: P
authors.lastname: Huehnchen
authors.forename: Andreas
authors.initials: A
authors.lastname: Hermann
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
authors.forename: Barbara
authors.initials: B
authors.lastname: Steiner
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D053687:Adult Stem Cells / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D004777:Environment; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D020267:MPTP Poisoning / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology / Q000534:rehabilitation*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D011509:Proteoglycans / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000941:Antigens; D001973:Bromodeoxyuridine; D002135:Calcium-Binding Proteins; D004298:Dopamine; D015259:Dopamine Agents; D049452:Green Fluorescent Proteins; D007381:Intermediate Filament Proteins; D007980:Levodopa; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D011509:Proteoglycans; D014446:Tyrosine 3-Monooxygenase; D000099216:Chondroitin Sulfate Proteoglycan 4; C491049:Aif1 protein, mouse; C577485:Nes protein, mouse