Rho Kinase Inhibition by Fasudil in the Striatal 6-Hydroxydopamine Lesion Mouse Model of Parkinson Disease
2014 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Rho Kinase Inhibition by Fasudil in the Striatal 6-Hydroxydopamine Lesion Mouse Model of Parkinson Disease
Tatenhorst, L. ; Tönges, L. ; Saal, K.-A. ; Koch, J. C. ; Szegő, É. M. ; Bähr, M. & Lingor, P. (2014)
Journal of Neuropathology and Experimental Neurology, 73(8) pp. 770-779. DOI: https://doi.org/10.1097/nen.0000000000000095
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- Authors
- Tatenhorst, Lars ; Tönges, Lars ; Saal, Kim-Ann ; Koch, J. C. ; Szegő, Éva M. ; Bähr, Mathias ; Lingor, Paul
- Abstract
- Chronic degeneration of nigrostriatal projections, followed by nigral dopaminergic cell death, is a key feature of Parkinson disease (PD). This study examines the neuroprotective potential of the rho kinase inhibitor fasudil in the 6-hydroxydopamine (6-OHDA) mouse model of PD in vivo. C57Bl/6 mice were lesioned by striatal stereotactic injections with 4 mu g of 6-OHDA and treated with fasudil 30 or 100 mg/kg body weight via drinking water. Motor behavior was tested biweekly; histologic and biochemical analyses were performed at 4 and 12 weeks after lesion. Motor behavior was severely impaired after 6-OHDA lesion and was not improved by fasudil treatment. Fasudil 100 mg/kg did not significantly increase the number of dopaminergic cells in the substantia nigra after 12 weeks versus lesion controls. Interestingly, however, high-performance liquid chromatography analysis of dopamine metabolites revealed that striatal levels of 3,4-dihydroxyphenylacetic acid were significantly increased after 12 weeks, suggesting a regenerative response. In contrast to recent findings in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin model, fasudil effects seem limited in this severe 6-OHDA model of PD. Nevertheless, high therapeutic concentrations of fasudil are suggestive of a proregenerative potential for dopaminergic neurons, making further evaluations of rho kinase inhibition as a proregenerative therapeutic strategy in PD promising.
- Issue Date
- 2014
- Journal
- Journal of Neuropathology and Experimental Neurology
- ISSN
- 0022-3069; 0022-3069
- eISSN
- 1554-6578
- Language
- English