Intrastriatal administration of erythropoietin protects dopaminergic neurons and improves neurobehavioral outcome in a rat model of Parkinson’s disease

Abstract Erythropoietin (EPO), a hematopoietic cytokine, has recently been demonstrated to protect nigral dopaminergic neurons in a mouse model of Parkinson’s disease (PD). In the present study, we tested the hypothesis that recombinant human erythropoietin (rhEPO) could protect dopaminergic neurons...

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Bibliographic Details
Published in:Neuroscience 2007-05, Vol.146 (3), p.1245-1258
Main Authors: Xue, Y.-Q, Zhao, L.-R, Guo, W.-P, Duan, W.-M
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents
Astrocytes - metabolism
Behavior, Animal - drug effects
Biological and medical sciences
Cell Count
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Densitometry
Dopamine - metabolism
Dopamine - physiology
Erythropoietin - administration & dosage
Erythropoietin - pharmacology
Erythropoietin - therapeutic use
Female
Fundamental and applied biological sciences. Psychology
Genes, MHC Class I - genetics
Genes, MHC Class II - genetics
immunocytochemistry
Immunohistochemistry
inflammation
Medical sciences
Microglia - metabolism
Microinjections
Neostriatum - metabolism
Neostriatum - physiology
Neurology
Neurons - pathology
neuroprotection
Neuroprotective Agents
Oxidopamine
Parkinson Disease, Secondary - drug therapy
Parkinson Disease, Secondary - pathology
Parkinson Disease, Secondary - psychology
Rats
Rats, Sprague-Dawley
Stereotyped Behavior - drug effects
striatum
substantia nigra
Substantia Nigra - pathology
tyrosine hydroxylase
Vertebrates: nervous system and sense organs
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Summary:Abstract Erythropoietin (EPO), a hematopoietic cytokine, has recently been demonstrated to protect nigral dopaminergic neurons in a mouse model of Parkinson’s disease (PD). In the present study, we tested the hypothesis that recombinant human erythropoietin (rhEPO) could protect dopaminergic neurons and improve neurobehavioral outcome in a rat model of PD. rhEPO (20 units in 2 μl of vehicle) was stereotaxically injected into one side of the striatum. 6-Hydroxydopamine (6-OHDA) was injected into the same side 1 day later. Another group of rats received rhEPO (5000 u/kg, i.p.) daily for 8 days, and unilateral injection of 6-OHDA in the striatum 3 days after systemic administration of rhEPO. We observed that intrastriatal administration, but not systemic administration of rhEPO significantly reduced the degree of rotational asymmetry. The rhEPO-treated rats also showed an improvement in skilled forelimb use when compared with control rats. The number of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons in the ipsilateral substantia nigra (SN) was significantly larger in intrastriatal rhEPO-treated rats than that in control rats. TH-IR fibers in the 6-OHDA-lesioned striatum were also increased in the intrastriatal rhEPO-treated rats when compared with control rats. In addition, there were lower levels of expression of major histocompatibility complex (MHC) class II antigens and a smaller number of activated microglia in the ipsilateral SN in intrastriatal rhEPO-treated rats than that in control rats at 2 weeks, suggesting that intrastriatal injection of rhEPO attenuated 6-OHDA-induced inflammation in the ipsilateral SN. Our results suggest that intrastriatal administration of rhEPO can protect nigral dopaminergic neurons from cell death induced by 6-OHDA and improve neurobehavioral outcome in a rat model of PD. Anti-inflammation may be one of mechanisms responsible for rhEPO neuroprotection.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2007.02.004