A Hematopoietic Growth Factor, Thrombopoietin, Has a Proapoptotic Role in the Brain

Central nervous and hematopoietic systems share developmental features. We report that thrombopoietin (TPO), a stimulator of platelet formation, acts in the brain as a counterpart of erythropoietin (EPO), a hematopoietic growth factor with neuroprotective properties. TPO is most prominent in postnat...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-01, Vol.102 (3), p.862-867
Main Authors: Ehrenreich, Hannelore, Hasselblatt, Martin, Knerlich, Friederike, von Ahsen, Nico, Jacob, Sonja, Sperling, Swetlana, Woldt, Helge, Vehmeyer, Katalin, Nave, Klaus-Armin, Sirén, Anna-Leena, Cerami, Anthony
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Astrocytes
Biological Sciences
Brain
Brain - cytology
Brain - metabolism
Brain Chemistry
Brain hypoxia
Cell death
Epics
Erythropoietin - physiology
Gene Expression Regulation
Hematopoietic Cell Growth Factors - physiology
Hypoxia - metabolism
MAP Kinase Signaling System
Messenger RNA
Mice
Mice, Inbred C57BL
Nerve Growth Factors - pharmacology
Neurology
Neurons
Neurons - cytology
Neurons - metabolism
Placebos
Prosencephalon - chemistry
Prosencephalon - cytology
Receptors
Rhombencephalon - chemistry
Rhombencephalon - cytology
Thrombopoietin - physiology
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Summary:Central nervous and hematopoietic systems share developmental features. We report that thrombopoietin (TPO), a stimulator of platelet formation, acts in the brain as a counterpart of erythropoietin (EPO), a hematopoietic growth factor with neuroprotective properties. TPO is most prominent in postnatal brain, whereas EPO is abundant in embryonic brain and decreases postnatally. Upon hypoxia, EPO and its receptor are rapidly reexpressed, whereas neuronal TPO and its receptor are down-regulated. Unexpectedly, TPO is strongly proapoptotic in the brain, causing death of newly generated neurons through the Ras-extracellular signal-regulated kinase 1/2 pathway. This effect is not only inhibited by EPO but also by neurotrophins. We suggest that the proapoptotic function of TPO helps to select for neurons that have acquired target-derived neurotrophic support.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0406008102