Nature Biotechnology
20, 1103 - 1110 (2002)
Published online: 15 October 2002; | doi:10.1038/nbt750
Neural stem cells display an inherent mechanism for rescuing dysfunctional neuronsJitka Ourednik1, 2, 5, 6, Václav Ourednik1, 2, 5, 6, William P. Lynch3, Melitta Schachner1, 4, 7
& Evan Y. Snyder2, 71
Department of Neurobiology, Swiss Federal Institute of Technology, Hoenggerberg, CH-8093, Switzerland. 2
Department of Neurology, Harvard Medical School, Harvard Institutes of Medicine, Boston, MA 02115, USA. 3
Department of Microbiology/Immunology, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272, USA. 4
Center for Molecular Neurobiology Hamburg, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. 5
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. 6
These authors contributed equally to this work. 7
These authors, ordered alphabetically, contributed equally to this work.
Correspondence should be addressed to Jitka Ourednik joured@iastate.edu or Evan Y. Snyder esnyder1@caregroup.harvard.eduWe investigated the hypothesis that neural stem cells (NSCs) possess an intrinsic capacity to "rescue" dysfunctional neurons in the brains of aged mice. The study focused on a neuronal cell type with stereotypical projections that is commonly compromised in the aged brain—the dopaminergic (DA) neuron. Unilateral implantation of murine NSCs into the midbrains of aged mice, in which the presence of stably impaired but nonapoptotic DA neurons was increased by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was associated with bilateral reconstitution of the mesostriatal system. Functional assays paralleled the spatiotemporal recovery of tyrosine hydroxylase (TH) and dopamine transporter (DAT) activity, which, in turn, mirrored the spatiotemporal distribution of donor-derived cells. Although spontaneous conversion of donor NSCs to TH+ cells contributed to nigral reconstitution in DA-depleted areas, the majority of DA neurons in the mesostriatal system were "rescued" host cells. Undifferentiated donor progenitors spontaneously expressing neuroprotective substances provided a plausible molecular basis for this finding. These observations suggest that host structures may benefit not only from NSC-derived replacement of lost neurons but also from the "chaperone" effect of some NSC-derived progeny.
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