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J Neurochem. 2015 Jul;134(2):261-75. doi: 10.1111/jnc.13102. Epub 2015 Apr 13.

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

Author information

1
Department of Neurology, University Medicine Göttingen, Göttingen, Germany.
2
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
3
Department of Neurology, Molecular Neurobiology Laboratory, Heinrich-Heine-University Medical Center Düsseldorf, Düsseldorf, Germany.
4
Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.

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 12 weeks after unilateral dorsal hemisection at Th8 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.

KEYWORDS:

axonal lesion; gene therapy; red nucleus; regeneration; rho kinase

PMID:
25807858
DOI:
10.1111/jnc.13102
[Indexed for MEDLINE]
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