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- Title
Potentiation of in vivo neuroprotection by BclX<sub>L</sub> and GDNF co-expression depends on post-lesion time in deafferentiated CNS neurons.
- Authors
Shevtsova, Z.; Malik, I.; Garrido, M.; Schöll, U.; Bähr, M.; Kügler, S.
- Abstract
To elucidate effective and long-lasting neuroprotective strategies, we analysed a combination of mitochondrial protection and neurotrophic support in two well-defined animal models of neurodegeneration, traumatic lesion of optic nerve and complete 6-hydroxydopamine (6-OHDA) lesion of nigrostriatal pathway. Neuroprotection by BclXL, Glial cell line-derived neurotrophic factor (GDNF) or BclXL plus GDNF co-expression were studied at 2 weeks and at 6–8 weeks after lesions. In both lesion paradigms, the efficacy of this combination approach significantly differed depending on post-lesion time. We show that BclXL expression is more important for neuronal survival in the early phase after lesions, whereas GDNF-mediated neuroprotection becomes more prominent in the advanced state of neurodegeneration. BclXL expression was not sufficient to finally inhibit degeneration of deafferentiated central nervous system neurons. Long-lasting GDNF-mediated neuroprotection depended on BclXL co-expression in the traumatic lesion paradigm, but was independent of BclXL in the 6-OHDA lesion model. The results demonstrate that neuroprotection studies in animal models of neurodegenerative diseases should generally be performed over extended periods of time in order to reveal the actual potency of a therapeutic approach.Gene Therapy (2006) 13, 1569–1578. doi:10.1038/sj.gt.3302822; published online 13 July 2006
- Subjects
MITOCHONDRIAL DNA; NEUROTROPHINS; NEURODEGENERATION; PARKINSON'S disease; GENETIC transformation; DOPAMINERGIC neurons
- Publication
Gene Therapy, 2006, Vol 13, Issue 22, p1569
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302822