Martin Köllensperger and Florian Krismer contributed equally to this work.
Erythropoietin is neuroprotective in a transgenic mouse model of multiple system atrophy†
Article first published online: 6 JAN 2011
Copyright © 2011 Movement Disorder Society
Volume 26, Issue 3, pages 507–515, 15 February 2011
How to Cite
Köllensperger, M., Krismer, F., Pallua, A., Stefanova, N., Poewe, W. and Wenning, G. K. (2011), Erythropoietin is neuroprotective in a transgenic mouse model of multiple system atrophy. Mov. Disord., 26: 507–515. doi: 10.1002/mds.23474
Relevant conflict of interest/financial disclosure: Nothing to report. The study was supported by MFI Grant 9441 and by FWF Grant P19989-B05. Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 31 MAR 2011
- Article first published online: 6 JAN 2011
- Manuscript Accepted: 13 SEP 2010
- Manuscript Revised: 16 JUN 2010
- Manuscript Received: 28 DEC 2009
Multiple system atrophy is a rapidly progressive neurodegenerative disorder with a markedly reduced life expectancy. Failure of symptomatic treatment raises an urgent need for disease-modifying strategies. We have investigated the neuroprotective potential of erythropoietin in (proteolipid protein)-α-synuclein transgenic mice exposed to 3-nitropropionic acid featuring multiple system atrophy-like pathology including oligodendroglial α-synuclein inclusions and selective neuronal degeneration.
Mice were treated with erythropoietin starting before (early erythropoietin) and after (late erythropoietin) intoxication with 3-nitropropionic acid. Nonintoxicated animals receiving erythropoietin and intoxicated animals treated with saline served as control groups. Behavioral tests included pole test, open field activity, and motor behavior scale. Immunohistochemistry for tyrosine hydroxylase and dopamine and cyclic adenosine monophosphate-regulated phosphoprotein (DARPP-32) was analyzed stereologically.
Animals receiving erythropoietin before and after 3-nitropropionic acid intoxication scored significantly lower on the motor behavior scale and they performed better in the pole test than controls with no significant difference between early and late erythropoietin administration. Similarly, rearing scores were worse in 3-nitropropionic acid-treated animals with no difference between the erythropoietin subgroups. Immunohistochemistry revealed significant attenuation of 3-nitropropionic acid-induced loss of tyrosine hydroxylase and DARPP-32 positive neurons in substantia nigra pars compacta and striatum, respectively, in both erythropoietin-treated groups without significant group difference in the substantia nigra. However, at striatal level, a significant difference between early and late erythropoietin administration was observed.
In the combined (proteolipid protein)-α-synuclein 3-nitropropionic acid multiple system atrophy mouse model, erythropoietin appears to rescue dopaminergic and striatal gabaergic projection neurons. This effect is associated with improved motor function. Further studies are warranted to develop erythropoietin as a potential interventional therapy in multiple system atrophy. © 2011 Movement Disorder Society