dc.contributor.author | Dass, B. | |
dc.contributor.author | Iravani, Mahmoud M. | |
dc.contributor.author | Huang, C. | |
dc.contributor.author | Barsoum, J. | |
dc.contributor.author | Engber, T. M. | |
dc.contributor.author | Galdes, A. | |
dc.contributor.author | Jenner, P. | |
dc.date.accessioned | 2013-06-27T08:01:54Z | |
dc.date.available | 2013-06-27T08:01:54Z | |
dc.date.issued | 2005-06 | |
dc.identifier.citation | Dass , B , Iravani , M M , Huang , C , Barsoum , J , Engber , T M , Galdes , A & Jenner , P 2005 , ' Sonic hedgehog delivered by an adeno-associated virus protects dopaminergic neurones against 6-OHDA toxicity in the rat ' , Journal of Neural Transmission , vol. 112 , no. 6 , pp. 763-778 . https://doi.org/10.1007/s00702-004-0227-7 | |
dc.identifier.issn | 0300-9564 | |
dc.identifier.other | ORCID: /0000-0002-4905-9682/work/32997591 | |
dc.identifier.uri | http://hdl.handle.net/2299/10975 | |
dc.description.abstract | 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 4 x 10(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 4 x 10(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 4 x 10(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. | en |
dc.format.extent | 16 | |
dc.language.iso | eng | |
dc.relation.ispartof | Journal of Neural Transmission | |
dc.subject | sonic hedgehog | |
dc.subject | adeno-associated virus | |
dc.subject | viral vector | |
dc.subject | 6-OHDA | |
dc.subject | substantia nigra | |
dc.subject | Parkinson's disease | |
dc.subject | MEDIATED GENE-TRANSFER | |
dc.subject | NEUROTROPHIC FACTOR | |
dc.subject | PARKINSONS-DISEASE | |
dc.subject | INTRASTRIATAL INJECTION | |
dc.subject | NIGROSTRIATAL SYSTEM | |
dc.subject | COMMON MARMOSETS | |
dc.subject | IN-VIVO | |
dc.subject | BEHAVIORAL IMPAIRMENT | |
dc.subject | FUNCTIONAL RECOVERY | |
dc.subject | PARTIAL LESIONS | |
dc.title | Sonic hedgehog delivered by an adeno-associated virus protects dopaminergic neurones against 6-OHDA toxicity in the rat | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Basic and Clinical Science Unit | |
dc.contributor.institution | Centre for Health Services and Clinical Research | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1007/s00702-004-0227-7 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |