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Comment
. 2004 Jul 6;101(27):10177-82.
doi: 10.1073/pnas.0401229101. Epub 2004 Jun 21.

No evidence for new dopaminergic neurons in the adult mammalian substantia nigra

Helena Frielingsdorf  1 , Katherine Schwarz, Patrik Brundin, Paul Mohapel
Affiliations
Comment

No evidence for new dopaminergic neurons in the adult mammalian substantia nigra

Helena Frielingsdorf et al. Proc Natl Acad Sci U S A. .

Abstract

A recent report by Zhao et al. [Zhao, M., Momma, S., Delfani, K., Carlen, M., Cassidy, R. M., Johansson, C. B., Brismar, H., Shupliakov, O., Frisen, J. & Janson, A. M. (2003) Proc. Natl. Acad. Sci. USA 100, 7925-7930] suggests that dopaminergic neurons, the cell type lost in Parkinson's disease, are continuously generated in the adult substantia nigra pars compacta. Using similar methodological procedures to label dividing cells, we found no evidence of new dopaminergic neurons in the substantia nigra, either in normal or 6-hydroxydopamine-lesioned hemi-Parkinsonian rodents, or even after growth factor treatment. Furthermore, we found no evidence of neural stem cells emanating from the cerebroventricular system and migrating to the substantia nigra. We conclude that it is unlikely that dopaminergic neurons are generated in the adult mammalian substantia nigra.

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Figures

Fig. 1.
Fig. 1.
Progenitor cells in the adult rodent SN do not display neuronal or dopaminergic phenotypes. (a) Distribution of BrdUrd (red) and TH (green) immunoreactive cells in the mouse SN after 21 days of BrdUrd (75 mg/ml) minipump infusion into the right lateral ventricle. (b) Laser confocal (Leica) image of a BrdUrd-labeled cell adjacent to a TH-labeled cell, viewed in three dimensions. Note that this is not a double-labeled cell because the orthogonal view reveals that the BrdUrd-labeled nucleus is not completely encapsulated by the TH-labeled cytoplasm. (c) Distribution of BrdUrd (red) and TH (green) immunoreactive cells in the 6-OHDA-lesioned rat SN after BDNF infusion (20). Note the dramatic reduction of TH-labeled cells in the SN as compared with the nonlesioned condition in a. (d) Confocal image of a BrdUrd-labeled cell adjacent to a TH-labeled cell from c. No BrdUrd+ cells coexpressed TH. (e) Confocal image of a red BrdUrd-labeled cell adjacent to a blue TH-labeled cell with its own green NeuN-labeled nucleus, demonstrating that the BrdUrd nucleus did not originate from the TH neuron. (Scale bar = 100 μmin a and c and 5 μm in b, d, and e.)
Fig. 2.
Fig. 2.
DiI acts as a retrograde tracer when injected i.c.v. (a) At 21 days after DiI injection i.c.v., labeling of the midbrain aqueduct is still evident, with very few cells observed in the adjacent parenchymal structures. Similar to striatal injections, i.c.v. DiI injections resulted in retrograde labeling of the major striatal afferent pathways: selective layers of the neocortex (b) and various thalamic nuclei (c) are shown. (d) Striatal DiI injections did not label the ependymal lining of the lateral ventricular wall. (e and g) A similar quantity of DiI (red) and TH (green) immunoreactive cells after either i.c.v. (e) or striatal (g) DiI injections. A three-dimensional laser confocal image of DiI incorporation into a TH cell (green) reveals no differences in the labeling pattern between i.c.v. (f) and striatal (h) DiI injections. Rats having their SN lesioned with 6-OHDA exhibit no DiI labeling, regardless of the injection location. (Scale bar = 100 μm in a–d, 20 μm in e, g, i, and j, and 5 μm in f and h.)
See this image and copyright information in PMC

Comment on

  • Evidence for neurogenesis in the adult mammalian substantia nigra.
    Zhao M, Momma S, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM. Zhao M, et al. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7925-30. doi: 10.1073/pnas.1131955100. Epub 2003 Jun 5. Proc Natl Acad Sci U S A. 2003. PMID: 12792021 Free PMC article.

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