AAV9-mediated erythropoietin gene delivery into the brain protects nigral dopaminergic neurons in a rat model of Parkinson's disease
| Autor: | Baofeng Ma, Duan Wm, Tatom Jb, R L Klein, Zhao Lr, Jiang Lx, YueQiang Xue, Li B |
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| Rok vydání: | 2009 |
| Předmět: |
Genetic Vectors
Central nervous system Substantia nigra Striatum Gene delivery Biology Pharmacology medicine.disease_cause Rats Sprague-Dawley Hydroxydopamines hemic and lymphatic diseases Genetics medicine Animals Erythropoietin Molecular Biology Adeno-associated virus Dopaminergic Gene Transfer Techniques Parkinson Disease Genetic Therapy Dependovirus Recombinant Proteins Rats Substantia Nigra medicine.anatomical_structure nervous system Immunology Erythrocyte Count Molecular Medicine Female Neuron medicine.drug |
| Zdroj: | Gene Therapy. 17:83-94 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/gt.2009.113 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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