SCA7 (Spinal Cerebellar Ataxia type 7) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion within the ataxin-7 gene. The main characteristics of the disorder include ataxia, retinal degeneration and loss of Purkinje and granule neurons of the cerebellum. Our research on SCA7 is focused on experiments to evaluate hypothesis that polyglutamine expanded ataxin-7 results in an altered Purkinje cell (PC) environment within the cerebellum. This altered environment specifically affects neurons that are involved in generating postural tone and coordinated movements. The corollary to this hypothesis is that if some or all of the specific components of the altered environment can be corrected, neurological function may improve and neurodegeneration may be prevented in SCA7 patients.
We deliver NASPM-an antagonist of the AMPA type glutamate receptor- to the mouse brain using a micro osmotic pump (Figure 1). Mice with pumps (Figure 2) in place were tested for motor performance on the Rotarod. There was no significant difference between animals implanted with NASPM or vehicle containing pumps after 14 or 28 days of continuous treatment. No animals manifested ill effect from treatment or catheter placement. These findings demonstrate that NASPM is well tolerated and has no detectable impact on baseline motor performance.
In order to determine if exogenous genes can be delivered to cells of the cerebellum, we performed stereotactic injections of a GFP expressing lentiviral vector. Mice were sacrificed by anesthetic overdose 1 week or 3 weeks following injection and perfused. Cryostat sections were mounted on slides and immunolabeled for GFP. Exogenous gene expression was induced by infection with lentivirus one week after injection (Figure 3) and spread to multiple folia by three weeks following a single inoculation (Figure 4).
Please click here if you are looking for the SCA7 R01 figures.
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