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2011 | 71 | 4 |
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Direct MRI-guided stereotaxic viral mediated gene transfer of alpha-synuclein in the Gottingen minipig CNS

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The aim was to establish a non-primate large animal PD model by lentiviral vector mediated mutant alpha-synuclein overexpression in the substantia nigra. Lentivirus encoding A53T alpha-synuclein (6 x 2.5 ^l) was stereotaxically injected into the substantia nigra of six adult female Gottingen minipigs. Contralateral control injections encoding enhanced green fluorescent protein (EGFP) were performed. Gait-analysis was performed pre- and postoperatively. PCR of the transgenes and immunohistochemical staining against alpha-synuclein, EGFP, GFAP and TH was performed after 20 weeks. Gait- analysis revealed a significant increase in step length and height, and a decrease in the double stand phase. PCR verified the mesencephalic presence of transgenes. IHC analysis showed alpha-synuclein expression in nigral neurons, around the injection tract and in related nigrostriatal projections. The alpha-synuclein positive neurons appeared swollen and vacuolated, in contrast to the EGFP-injected control side. To transduct all nigrostriatal cells with few microinjections, wider dissemination of the transgene must be achieved.
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  • Institute of Biomedicine, Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
  • Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark
  • Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, University of Aarhus, Tjele, Denmark
  • Institute of Biomedicine, Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
  • Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark
  • Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, University of Aarhus, Tjele, Denmark
  • Institute of Biomedicine, Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
  • Hammel Neurorehabilitation Centre, Hamme, Denmark
  • Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, University of Aarhus, Tjele, Denmark
  • Institute of Biomedicine, Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
  • Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark
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