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

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Glud A. N., Hedegaard C., Nielsen M. S., Sorensen J. C., Bendixen C., Jensen P. H., Mogensen P. H., Larsen K., Bjarkam C. R.

Acta Neurobiologiae Experimentalis

2011

tom 71

nr 4

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.

Ograniczanie wyników

1 Acta Neurobiologiae Experimentalis

1 Bendixen C.

1 Bjarkam C. R.

1 Glud A. N.

1 Hedegaard C.

1 Jensen P. H.

1 Larsen K.

1 Mogensen P. H.

1 Nielsen M. S.

1 Sorensen J. C.

1 2011

Wyniki wyszukiwania

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