Abstract |
We have recently shown that intrastriatal injection of recombinant human erythropoietin (EPO) protects dopaminergic (DA) neurons in the substantia nigra (SN) from 6-hydroxydopamine (6-OHDA) toxicity in a rat model of Parkinson's disease. However, systemic administration of EPO did not protect nigral DA neurons, suggesting that the blood-brain barrier limits the passage of EPO protein into the brain. In the present study, we used an adeno-associated viral (AAV) serotype 9 (AAV9) vector to deliver the human EPO gene into the brain of 6-OHDA-lesioned rats. We observed that expression of the human EPO gene was robust and stable in the striatum and the SN for up to 10 weeks. EPO-immunoreactive (IR) cells were widespread throughout the injected striatum, and EPO-IR neurons and fibers were also found in the ipsilateral SN. Enzyme-linked immunosorbent assay and western blot analyses exhibited dramatic levels of EPO protein in the injected striatum. As a result, nigral DA neurons were protected against 6-OHDA-induced toxicity. Amphetamine-induced rotational asymmetry and spontaneous forelimb use asymmetry were both attenuated. Interestingly, we also observed that intrastriatal injection of AAV9-EPO vectors led to increased numbers of red blood cells in peripheral blood. This highlights the importance of using an inducible gene delivery system for EPO gene delivery.
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Authors | Y-Q Xue, B-F Ma, L-R Zhao, J B Tatom, B Li, L-X Jiang, R L Klein, W-M Duan |
Journal | Gene therapy
(Gene Ther)
Vol. 17
Issue 1
Pg. 83-94
(Jan 2010)
ISSN: 1476-5462 [Electronic] England |
PMID | 19727138
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Hydroxydopamines
- Recombinant Proteins
- Erythropoietin
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Topics |
- Animals
- Dependovirus
(genetics)
- Erythrocyte Count
- Erythropoietin
(genetics)
- Female
- Gene Transfer Techniques
- Genetic Therapy
- Genetic Vectors
- Hydroxydopamines
(metabolism)
- Parkinson Disease
(therapy)
- Rats
- Rats, Sprague-Dawley
- Recombinant Proteins
- Substantia Nigra
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