AAV-mediated expression of BAG1 and ROCK2-shRNA promote neuronal survival and axonal sprouting in a rat model of rubrospinal tract injury

2015 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​AAV-mediated expression of BAG1 and ROCK2-shRNA promote neuronal survival and axonal sprouting in a rat model of rubrospinal tract injury​
Challagundla, M.; Koch, J. C. ; Ribas, V. T. ; Michel, U. ; Kügler, S. ; Ostendorf, T. & Bradke, F. et al.​ (2015) 
Journal of Neurochemistry134(2) pp. 261​-275​.​ DOI: https://doi.org/10.1111/jnc.13102 

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Authors
Challagundla, Malleswari; Koch, Jan Christoph ; Ribas, Vinicius Toledo ; Michel, Uwe ; Kügler, Sebastian ; Ostendorf, Thomas; Bradke, Frank; Müller, H. W.; Bähr, M. ; Lingor, Paul 
Abstract
A lesion to the rat rubrospinal tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the rubrospinal tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the rubrospinal tract, and motor recovery 12weeks after unilateral dorsal hemisection at Th-8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion.
Issue Date
2015
Journal
Journal of Neurochemistry 
ISSN
0022-3042
eISSN
1471-4159
Language
English

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