Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons

Jitka Ourednik, Václav Ourednik, William P. Lynch, Melitta Schachner, Evan Y. Snyder

Research output: Contribution to journalArticle

414 Citations (Scopus)

Abstract

We 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.

Original languageEnglish (US)
Pages (from-to)1103-1110
Number of pages8
JournalNature biotechnology
Volume20
Issue number11
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Neural Stem Cells
Stem cells
Neurons
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Brain
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine Plasma Membrane Transport Proteins
Substantia Nigra
Mesencephalon
Assays
Recovery

All Science Journal Classification (ASJC) codes

  • Applied Microbiology and Biotechnology
  • Bioengineering
  • Molecular Medicine
  • Biotechnology
  • Biomedical Engineering

Cite this

Ourednik, Jitka ; Ourednik, Václav ; Lynch, William P. ; Schachner, Melitta ; Snyder, Evan Y. / Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. In: Nature biotechnology. 2002 ; Vol. 20, No. 11. pp. 1103-1110.
@article{ddc18ae1dd594d189c445ca20868b8fc,
title = "Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons",
abstract = "We 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.",
author = "Jitka Ourednik and V{\'a}clav Ourednik and Lynch, {William P.} and Melitta Schachner and Snyder, {Evan Y.}",
year = "2002",
month = "1",
day = "1",
doi = "https://doi.org/10.1038/nbt750",
language = "English (US)",
volume = "20",
pages = "1103--1110",
journal = "Nature Biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "11",

}

Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. / Ourednik, Jitka; Ourednik, Václav; Lynch, William P.; Schachner, Melitta; Snyder, Evan Y.

In: Nature biotechnology, Vol. 20, No. 11, 01.01.2002, p. 1103-1110.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons

AU - Ourednik, Jitka

AU - Ourednik, Václav

AU - Lynch, William P.

AU - Schachner, Melitta

AU - Snyder, Evan Y.

PY - 2002/1/1

Y1 - 2002/1/1

N2 - We 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.

AB - We 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.

UR - http://www.scopus.com/inward/record.url?scp=0036844019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036844019&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/nbt750

DO - https://doi.org/10.1038/nbt750

M3 - Article

C2 - 12379867

VL - 20

SP - 1103

EP - 1110

JO - Nature Biotechnology

JF - Nature Biotechnology

SN - 1087-0156

IS - 11

ER -