 |
 Previous Article | Next Article 
The Journal of Neuroscience, December 15, 2001, 21(24):9733-9743
Erythropoietin Regulates the In Vitro and In
Vivo Production of Neuronal Progenitors by Mammalian Forebrain
Neural Stem Cells
Tetsuro
Shingo,
S. Todd
Sorokan,
Takuya
Shimazaki, and
Samuel
Weiss
Genes & Development Research Group, Department of Cell Biology and
Anatomy, University of Calgary, Faculty of Medicine, Calgary, Alberta,
Canada T2N 4N1
Recent studies have shown that neurogenesis is enhanced after
hypoxia and that erythropoietin (EPO), an inducible cytokine, is
produced in the brain as part of the intrinsic hypoxia response. Thus,
we asked whether EPO might regulate neurogenesis by forebrain neural
stem cells (NSCs). We found that EPO receptors are expressed in the
embryonic germinal zone during neurogenesis as well as in the adult
subventricular zone, which continues to generate neurons throughout
adulthood. Cultured NSCs exposed to a modest hypoxia produced two- to
threefold more neurons, which was associated with an elevation in EPO
gene expression. The enhanced neuron production attributable to hypoxia
was mimicked by EPO and blocked by coadministration of an EPO
neutralizing antibody. EPO appears to act directly on NSCs, promoting
the production of neuronal progenitors at the expense of multipotent
progenitors. EPO infusion into the adult lateral ventricles resulted in
a decrease in the numbers of NSCs in the subventricular zone, an
increase in newly generated cells migrating to the olfactory bulb, and
an increase in new olfactory bulb interneurons. Infusion of anti-EPO
antibodies had the opposite effect: an increase in the number of NSCs
in the subventricular zone and a decrease in the number of newly generated cells migrating to the bulb. These findings suggest that EPO
is an autocrine-paracrine factor, capable of regulating the production
of neuronal progenitor cells by forebrain NSCs.
Key words:
neural stem cells; erythropoietin; neuronal progenitors; neurogenesis; differentiation; Mash1; NF- B
Copyright © 2001 Society for Neuroscience 0270-6474/01/21249733-11$05.00/0
This article has been cited by other articles:
|
|
|
|
 
C. Bartels, K. Spate, H. Krampe, and H. Ehrenreich
Review: Recombinant human erythropoietin: novel strategies for neuroprotective/neuroregenerative treatment of multiple sclerosis
Therapeutic Advances in Neurological Disorders,
November 1, 2008;
1(3):
193 - 206.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Rabie and H. H. Marti
Brain Protection by Erythropoietin: A Manifold Task
Physiology,
October 1, 2008;
23(5):
263 - 274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Joyeux-Faure
Cellular Protection by Erythropoietin: New Therapeutic Implications?
J. Pharmacol. Exp. Ther.,
December 1, 2007;
323(3):
759 - 762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Wang, Z. G. Zhang, S. R. Gregg, R. L. Zhang, Z. Jiao, Y. LeTourneau, X. Liu, Y. Feng, J. Gerwien, L. Torup, et al.
The Sonic Hedgehog Pathway Mediates Carbamylated Erythropoietin-enhanced Proliferation and Differentiation of Adult Neural Progenitor Cells
J. Biol. Chem.,
November 2, 2007;
282(44):
32462 - 32470.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. E. B. Nickerson, J. G. Emsley, T. Myers, and D. B. Clarke
Proliferation and Expression of Progenitor and Mature Retinal Phenotypes in the Adult Mammalian Ciliary Body after Retinal Ganglion Cell Injury
Invest. Ophthalmol. Vis. Sci.,
November 1, 2007;
48(11):
5266 - 5275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ehrenreich, B. Fischer, C. Norra, F. Schellenberger, N. Stender, M. Stiefel, A.-L. Siren, W. Paulus, K.-A. Nave, R. Gold, et al.
Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis
Brain,
October 1, 2007;
130(10):
2577 - 2588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Iwai, G. Cao, W. Yin, R. A. Stetler, J. Liu, and J. Chen
Erythropoietin Promotes Neuronal Replacement Through Revascularization and Neurogenesis After Neonatal Hypoxia/Ischemia in Rats
Stroke,
October 1, 2007;
38(10):
2795 - 2803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-Y. Chen, P. Asavaritikrai, J. T. Prchal, and C. T. Noguchi
Endogenous Erythropoietin Signaling Is Required for Normal Neural Progenitor Cell Proliferation
J. Biol. Chem.,
August 31, 2007;
282(35):
25875 - 25883.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Jomura, M. Uy, K. Mitchell, R. Dallasen, C. J. Bode, and Y. Xu
Potential Treatment of Cerebral Global Ischemia with Oct-4+ Umbilical Cord Matrix Cells
Stem Cells,
January 1, 2007;
25(1):
98 - 106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H. L. Teh, K. K. Y. Lam, C. C. Loh, J. M. Loo, T. Yan, and T. M. Lim
Neuronal PAS Domain Protein 1 Is a Transcriptional Repressor and Requires Arylhydrocarbon Nuclear Translocator for Its Nuclear Localization
J. Biol. Chem.,
November 10, 2006;
281(45):
34617 - 34629.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Chavez, O. Baranova, J. Lin, and P. Pichiule
The Transcriptional Activator Hypoxia Inducible Factor 2 (HIF-2/EPAS-1) Regulates the Oxygen-Dependent Expression of Erythropoietin in Cortical Astrocytes
J. Neurosci.,
September 13, 2006;
26(37):
9471 - 9481.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Bierer, M. C. Peceny, C. H. Hartenberger, and R. K. Ohls
Erythropoietin Concentrations and Neurodevelopmental Outcome in Preterm Infants
Pediatrics,
September 1, 2006;
118(3):
e635 - e640.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Pacary, H. Legros, S. Valable, P. Duchatelle, M. Lecocq, E. Petit, O. Nicole, and M. Bernaudin
Synergistic effects of CoCl2 and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells
J. Cell Sci.,
July 1, 2006;
119(13):
2667 - 2678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Wang, Z. G. Zhang, R. L. Zhang, S. R. Gregg, A. Hozeska-Solgot, Y. LeTourneau, Y. Wang, and M. Chopp
Matrix metalloproteinase 2 (MMP2) and MMP9 secreted by erythropoietin-activated endothelial cells promote neural progenitor cell migration.
J. Neurosci.,
May 31, 2006;
26(22):
5996 - 6003.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Um and H. F. Lodish
Antiapoptotic Effects of Erythropoietin in Differentiated Neuroblastoma SH-SY5Y Cells Require Activation of Both the STAT5 and AKT Signaling Pathways
J. Biol. Chem.,
March 3, 2006;
281(9):
5648 - 5656.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-L. Siren, K. Radyushkin, S. Boretius, D. Kammer, C.-C. Riechers, O. Natt, D. Sargin, T. Watanabe, S. Sperling, T. Michaelis, et al.
Global brain atrophy after unilateral parietal lesion and its prevention by erythropoietin
Brain,
February 1, 2006;
129(2):
480 - 489.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. T. Tsai, J. J. Ohab, N. Kertesz, M. Groszer, C. Matter, J. Gao, X. Liu, H. Wu, and S. T. Carmichael
A Critical Role of Erythropoietin Receptor in Neurogenesis and Post-Stroke Recovery
J. Neurosci.,
January 25, 2006;
26(4):
1269 - 1274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Munoz, B. R. Stoutenger, A. P. Robinson, J. L. Spees, and D. J. Prockop
Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice
PNAS,
December 13, 2005;
102(50):
18171 - 18176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Zhang, Z. G. Zhang, and M. Chopp
Neurogenesis in the Adult Ischemic Brain: Generation, Migration, Survival, and Restorative Therapy
Neuroscientist,
October 1, 2005;
11(5):
408 - 416.
[Abstract]
[PDF]
|
|
|
|
|
|
|
L. Belayev, L. Khoutorova, W. Zhao, A. Vigdorchik, A. Belayev, R. Busto, E. Magal, and M. D. Ginsberg
Neuroprotective Effect of Darbepoetin Alfa, a Novel Recombinant Erythropoietic Protein, in Focal Cerebral Ischemia in Rats
Stroke,
May 1, 2005;
36(5):
1065 - 1070.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. N. Abrous, M. Koehl, and M. Le Moal
Adult Neurogenesis: From Precursors to Network and Physiology
Physiol Rev,
April 1, 2005;
85(2):
523 - 569.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ehrenreich, M. Hasselblatt, F. Knerlich, N. von Ahsen, S. Jacob, S. Sperling, H. Woldt, K. Vehmeyer, K.-A. Nave, and A.-L. Siren
A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain
PNAS,
January 18, 2005;
102(3):
862 - 867.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Maiese, F. Li, and Z. Z. Chong
New Avenues of Exploration for Erythropoietin
JAMA,
January 5, 2005;
293(1):
90 - 95.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. G. Kuhn, C. Cooper-Kuhn, P. Eriksson, and M. Nilsson
Signals Regulating Neurogenesis in the Adult Olfactory Bulb
Chem Senses,
January 1, 2005;
30(suppl_1):
i109 - i110.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Ohls, R. A. Ehrenkranz, A. Das, A. M. Dusick, K. Yolton, E. Romano, V. Delaney-Black, L.-A. Papile, N. P. Simon, J. J. Steichen, et al.
Neurodevelopmental Outcome and Growth at 18 to 22 Months' Corrected Age in Extremely Low Birth Weight Infants Treated With Early Erythropoietin and Iron
Pediatrics,
November 1, 2004;
114(5):
1287 - 1291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Wong and A. J. Van der Kogel
MECHANISMS OF RADIATION INJURY TO THE CENTRAL NERVOUS SYSTEM: IMPLICATIONS FOR NEUROPROTECTION
Mol. Interv.,
October 1, 2004;
4(5):
273 - 284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Sinor and L. Lillien
Akt-1 Expression Level Regulates CNS Precursors
J. Neurosci.,
September 29, 2004;
24(39):
8531 - 8541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Enwere, T. Shingo, C. Gregg, H. Fujikawa, S. Ohta, and S. Weiss
Aging Results in Reduced Epidermal Growth Factor Receptor Signaling, Diminished Olfactory Neurogenesis, and Deficits in Fine Olfactory Discrimination
J. Neurosci.,
September 22, 2004;
24(38):
8354 - 8365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bani-Yaghoub, S. E. Kendall, D. P. Moore, S. Bellum, R. A. Cowling, G. N. Nikopoulos, C. J. Kubu, C. Vary, and J. M. Verdi
Insulin acts as a myogenic differentiation signal for neural stem cells with multilineage differentiation potential
Development,
September 1, 2004;
131(17):
4287 - 4298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Acker and H. Acker
Cellular oxygen sensing need in CNS function: physiological and pathological implications
J. Exp. Biol.,
August 15, 2004;
207(18):
3171 - 3188.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. H. Marti
Erythropoietin and the hypoxic brain
J. Exp. Biol.,
August 15, 2004;
207(18):
3233 - 3242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A Bogoyevitch
An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection
Cardiovasc Res,
August 1, 2004;
63(2):
208 - 216.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Wang, Z. Zhang, Y. Wang, R. Zhang, and M. Chopp
Treatment of Stroke With Erythropoietin Enhances Neurogenesis and Angiogenesis and Improves Neurological Function in Rats
Stroke,
July 1, 2004;
35(7):
1732 - 1737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T Strunk, C Hartel, and C Schultz
Does erythropoietin protect the preterm brain?
Arch. Dis. Child. Fetal Neonatal Ed.,
July 1, 2004;
89(4):
F364 - F366.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Hirabayashi, Y. Itoh, H. Tabata, K. Nakajima, T. Akiyama, N. Masuyama, and Y. Gotoh
The Wnt/{beta}-catenin pathway directs neuronal differentiation of cortical neural precursor cells
Development,
June 15, 2004;
131(12):
2791 - 2801.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gregg and S. Weiss
Generation of Functional Radial Glial Cells by Embryonic and Adult Forebrain Neural Stem Cells
J. Neurosci.,
December 17, 2003;
23(37):
11587 - 11601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Moon, M. Krawczyk, D. Ahn, I. Ahmet, D. Paik, E. G. Lakatta, and M. I. Talan
Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats
PNAS,
September 30, 2003;
100(20):
11612 - 11617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Imitola, E. Y. Snyder, and S. J. Khoury
Genetic programs and responses of neural stem/progenitor cells during demyelination: potential insights into repair mechanisms in multiple sclerosis
Physiol Genomics,
August 15, 2003;
14(3):
171 - 197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Erbayraktar, G. Grasso, A. Sfacteria, Q.-w. Xie, T. Coleman, M. Kreilgaard, L. Torup, T. Sager, Z. Erbayraktar, N. Gokmen, et al.
Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo
PNAS,
May 27, 2003;
100(11):
6741 - 6746.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Calvillo, R. Latini, J. Kajstura, A. Leri, P. Anversa, P. Ghezzi, M. Salio, A. Cerami, and M. Brines
Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling
PNAS,
April 15, 2003;
100(8):
4802 - 4806.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Guillard, S. Chretien, A.-S. Pelus, F. Porteu, O. Muller, P. Mayeux, and V. Duprez
Activation of the Mitogen-activated Protein Kinases Erk1/2 by Erythropoietin Receptor via a Gi Protein beta gamma -Subunit-initiated Pathway
J. Biol. Chem.,
March 21, 2003;
278(13):
11050 - 11056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Shingo, C. Gregg, E. Enwere, H. Fujikawa, R. Hassam, C. Geary, J. C. Cross, and S. Weiss
Pregnancy-Stimulated Neurogenesis in the Adult Female Forebrain Mediated by Prolactin
Science,
January 3, 2003;
299(5603):
117 - 120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Jin, Y. Zhu, Y. Sun, X. O. Mao, L. Xie, and D. A. Greenberg
Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo
PNAS,
September 3, 2002;
99(18):
11946 - 11950.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Gorio, N. Gokmen, S. Erbayraktar, O. Yilmaz, L. Madaschi, C. Cichetti, A. M. Di Giulio, E. Vardar, A. Cerami, and M. Brines
Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma
PNAS,
July 9, 2002;
99(14):
9450 - 9455.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
