Show simple item record

dc.contributor.authorDass, B.
dc.contributor.authorIravani, Mahmoud M.
dc.contributor.authorHuang, C.
dc.contributor.authorBarsoum, J.
dc.contributor.authorEngber, T. M.
dc.contributor.authorGaldes, A.
dc.contributor.authorJenner, P.
dc.date.accessioned2013-06-27T08:01:54Z
dc.date.available2013-06-27T08:01:54Z
dc.date.issued2005-06
dc.identifier.citationDass , 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.issn0300-9564
dc.identifier.otherPURE: 735504
dc.identifier.otherPURE UUID: d4eb8d34-8415-426c-bb4a-ec2d6b444a72
dc.identifier.otherWOS: 000229905800003
dc.identifier.otherScopus: 18544366978
dc.identifier.otherORCID: /0000-0002-4905-9682/work/32997591
dc.identifier.urihttp://hdl.handle.net/2299/10975
dc.description.abstractDirect 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.extent16
dc.language.isoeng
dc.relation.ispartofJournal of Neural Transmission
dc.subjectsonic hedgehog
dc.subjectadeno-associated virus
dc.subjectviral vector
dc.subject6-OHDA
dc.subjectsubstantia nigra
dc.subjectParkinson's disease
dc.subjectMEDIATED GENE-TRANSFER
dc.subjectNEUROTROPHIC FACTOR
dc.subjectPARKINSONS-DISEASE
dc.subjectINTRASTRIATAL INJECTION
dc.subjectNIGROSTRIATAL SYSTEM
dc.subjectCOMMON MARMOSETS
dc.subjectIN-VIVO
dc.subjectBEHAVIORAL IMPAIRMENT
dc.subjectFUNCTIONAL RECOVERY
dc.subjectPARTIAL LESIONS
dc.titleSonic hedgehog delivered by an adeno-associated virus protects dopaminergic neurones against 6-OHDA toxicity in the raten
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionNeurodegenerative Diseases
dc.contributor.institutionAgriculture, Veterinary and Food Sciences
dc.description.statusPeer reviewed
rioxxterms.versionofrecordhttps://doi.org/10.1007/s00702-004-0227-7
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record