University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Centre for Neuroscience
  • Centre for Neuroscience - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Centre for Neuroscience
  • Centre for Neuroscience - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Cell intrinsic and extrinsic factors contribute to enhance neural circuit reconstruction following transplantation in Parkinsonian mice

    Thumbnail
    Citations
    Scopus
    Web of Science
    Altmetric
    22
    22
    Author
    Kauhausen, J; Thompson, LH; Parish, CL
    Date
    2013-01-01
    Source Title
    JOURNAL OF PHYSIOLOGY-LONDON
    Publisher
    WILEY
    University of Melbourne Author/s
    Kauhausen, Jessica; Parish, Clare; Thompson, Lachlan; Kauhausen, Jessica
    Affiliation
    Centre For Neuroscience Research
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Kauhausen, J., Thompson, L. H. & Parish, C. L. (2013). Cell intrinsic and extrinsic factors contribute to enhance neural circuit reconstruction following transplantation in Parkinsonian mice. JOURNAL OF PHYSIOLOGY-LONDON, 591 (1), pp.77-91. https://doi.org/10.1113/jphysiol.2012.243063.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/33273
    DOI
    10.1113/jphysiol.2012.243063
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630773
    NHMRC Grant code
    NHMRC/566582
    NHMRC/628542
    NHMRC/1022637
    Description

    C1 - Journal Articles Refereed

    Abstract
    Cell replacement therapy for Parkinson's disease has predominantly focused on ectopic transplantation of fetal dopamine (DA) neurons into the striatum as a means to restore neurotransmission, rather than homotopic grafts into the site of cell loss, which would require extensive axonal growth. However, ectopic grafts fail to restore important aspects of DA circuitry necessary for controlled basal ganglia output, and this may underlie the suboptimal and variable functional outcomes in patients. We recently showed that DA neurons in homotopic allografts of embryonic ventral mesencephalon (VM) can send long axonal projections along the nigrostriatal pathway in order to innervate forebrain targets, although the extent of striatal reinnervation remains substantially less than can be achieved with ectopic placement directly into the striatal target. Here, we examined the possible benefits of using younger VM donor tissue and over-expression of glial cell-derived neurotrophic factor (GDNF) in the striatal target to improve the degree of striatal innervation from homotopic grafts. Younger donor tissue, collected on embryonic day (E)10, generated 4-fold larger grafts with greater striatal targeting, compared to grafts generated from more conventional E12 donor VM. Over-expression of GDNF in the host brain also significantly increased DA axonal growth and striatal innervation. Furthermore, a notable increase in the number and proportion of A9 DA neurons, essential for functional recovery, was observed in younger donor grafts treated with GDNF. Behavioural testing confirmed functional integration of younger donor tissue and demonstrated that improved motor function could be attributed to both local midbrain and striatal innervation. Together, these findings suggest there is significant scope for further development of intra-nigral grafting as a restorative approach for Parkinson's disease.
    Keywords
    Neurology and Neuromuscular Diseases; Regenerative Medicine (incl. Stem Cells and Tissue Engineering); Nervous System and Disorders

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45689]
    • Centre for Neuroscience - Research Publications [86]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors