title: The majority of newly generated cells in the adult mouse substantia nigra express low levels of Doublecortin, but their proliferation is unaffected by 6-OHDA-induced nigral lesion or Minocycline-mediated inhibition of neuroinflammation.
abstract: Parkinson's disease is characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN). However, whether regenerative endogenous neurogenesis is taking place in the mammalian SN of parkinsonian and non-parkinsonian brains remains of debate. Here, we tested whether proliferating cells in the SN and their neurogenic potential would be affected by anti-inflammatory treatment under physiological conditions and in the 6-hydroxy-dopamine (6-OHDA) Parkinson's disease mouse model. We report that the majority of newly generated nigral cells are positive for Doublecortin (Dcx), which is an often used marker for neural progenitor cells. Yet, Dcx expression levels in these cells were much lower than in neural progenitor cells of the subventricular zone and the dentate gyrus neural progenitor cells. Furthermore, these newly generated nigral cells are negative for neuronal lineage markers such as TuJ1 and NeuN. Therefore, their neuronal commitment is questionable. Instead, we found evidence for oligodendrogenesis and astrogliosis in the SN. Finally, neither short-term nor long-term inhibition of neuroinflammation by Minocycline- or 6-OHDA-induced lesion affected the numbers of newly generated cells in our disease paradigm. Our findings of adult generated Dcx(+) cells in the SN add important data for understanding the cellular composition and consequently the regenerative capacity of the SN.
authors.affiliation: Institute of Cell Biology, Stem Cell Biology and Regeneration Group, Münster, Germany.
authors.forename: Maik M A
authors.initials: MM
authors.lastname: Worlitzer
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
authors.forename: Jens C
authors.initials: JC
authors.lastname: Schwamborn
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D049109:Cell Proliferation; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008911:Minocycline / Q000494:pharmacology; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016627:Oxidopamine; D008911:Minocycline
keywords: 6-hydroxydopamine; Parkinson's disease; neurogenesis; oligodendrogenesis