Source:http://linkedlifedata.com/resource/pubmed/id/15586304
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2005-5-3
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| pubmed:abstractText |
Direct intracerebral administration of sonic hedgehog (SHH) reduces 6-OHDA and MPTP toxicity to nigral dopaminergic cells in rats and primates. To determine whether transfection of the DNA sequence for SHH using viral vectors also protects against 6-OHDA toxicity, a type 2 adeno- associated virus (AAV) incorporating 600 base pairs of N-terminal SHH DNA was generated to induce SHH expression in rat striatum.AAV-SHH was injected into the striatum, 3 weeks prior to the initiation of an unilateral partial 6-OHDA nigro-striatal lesion. Animals receiving 4x10(7) viral particles of AAV-SHH showed a reduction in (+)-amphetamine induced ipsilateral turning over 4 weeks, when compared to animals receiving vehicle or a LacZ encoding vector. Following vehicle or AAV-LacZ administration, 6-OHDA caused a marked loss of striatal dopamine content and nigral tyrosine hydroxylase (TH) immunopositive cells. Following treatment with 4x10(7) viral particles of AAV-SHH the loss of striatal dopamine content was reduced and there was marked preservation of nigral dopaminergic cells. However, administration of 4x10(8) particles of AAV-SHH did not cause a significant change in (+)-amphetamine-induced rotation, striatal dopamine levels or the number of nigral TH immunoreactive cells following 6-OHDA lesioning compared to vehicle or AAV-LacZ treated animals. The results show that SHH delivered via a viral vector can protect dopaminergic neurons against 6-OHDA toxicity and suggest that this could be developed into a novel treatment for PD. However, the effects maybe dose limited due to uncoupling of hedgehog receptor signalling at higher levels of SHH expression.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Hedgehog Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/SHH protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0300-9564
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
112
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
763-78
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| pubmed:dateRevised |
2009-11-3
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| pubmed:meshHeading |
pubmed-meshheading:15586304-Adenoviridae,
pubmed-meshheading:15586304-Adrenergic Agents,
pubmed-meshheading:15586304-Animals,
pubmed-meshheading:15586304-Corpus Striatum,
pubmed-meshheading:15586304-Dopamine,
pubmed-meshheading:15586304-Genetic Vectors,
pubmed-meshheading:15586304-Hedgehog Proteins,
pubmed-meshheading:15586304-Humans,
pubmed-meshheading:15586304-Immunohistochemistry,
pubmed-meshheading:15586304-Injections, Intraventricular,
pubmed-meshheading:15586304-Male,
pubmed-meshheading:15586304-Nerve Degeneration,
pubmed-meshheading:15586304-Neurons,
pubmed-meshheading:15586304-Neuroprotective Agents,
pubmed-meshheading:15586304-Oxidopamine,
pubmed-meshheading:15586304-Polymerase Chain Reaction,
pubmed-meshheading:15586304-Rats,
pubmed-meshheading:15586304-Rats, Sprague-Dawley,
pubmed-meshheading:15586304-Trans-Activators,
pubmed-meshheading:15586304-Transfection,
pubmed-meshheading:15586304-Tyrosine 3-Monooxygenase
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| pubmed:year |
2005
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| pubmed:articleTitle |
Sonic hedgehog delivered by an adeno-associated virus protects dopaminergic neurones against 6-OHDA toxicity in the rat.
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| pubmed:affiliation |
Neurodegenerative Diseases Research Centre, GKT School of Biomedical Sciences, King's College, London, United Kingdom.
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| pubmed:publicationType |
Journal Article
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