Bioluminescence‐driven optogenetic activation of transplanted neural precursor cells improves motor deficits in a Parkinson's disease mouse model
Autor: | Tariq M. Brown, Nicolai Dorka, Mansi Prakash, Jessica R. Zenchak, William E. Medendorp, Lina Marie Wagner, Ute Hochgeschwender, Brandon Palmateer, Eric D. Petersen |
---|---|
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Parkinson's disease medicine.medical_treatment Population Mice Transgenic Motor Activity Optogenetics Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Neural Stem Cells Precursor cell Animals Medicine education education.field_of_study Luminescent Agents Opsins business.industry Imidazoles Parkinson Disease Stem-cell therapy medicine.disease Embryonic stem cell Transplantation Disease Models Animal Luminescent Proteins 030104 developmental biology Pyrazines Rotarod Performance Test Luminescent Measurements Female Stem cell business Neuroscience 030217 neurology & neurosurgery |
Zdroj: | J Neurosci Res |
ISSN: | 1097-4547 0360-4012 |
Popis: | The need to develop efficient therapies for neurodegenerative diseases is urgent, especially given the increasing percentages of the population living longer, with increasing chances of being afflicted with conditions like Parkinson’s Disease (PD). A promising curative approach toward PD and other neurodegenerative diseases is the transplantation of stem cells to halt and potentially reverse neuronal degeneration. However, stem cell therapy does not consistently lead to improvement for patients. By using remote stimulation to optogenetically activate transplanted cells we attempted to improve behavioral outcomes of stem cell transplantation. We generated a neuronal precursor cell line expressing luminopsin 3 (LMO3), a luciferase-channelrhodopsin fusion protein, which responds to the luciferase substrate coelenterazine (CTZ) with emission of blue light that in turn activates the opsin. Neuronal precursor cells were injected bilaterally into the striatum of homozygous aphakia mice, which carry a spontaneous mutation leading to lack of dopaminergic neurons and symptoms of PD. Following transplantation, the cells were stimulated over a period of 10 days by intraventricular injections of CTZ. Mice receiving CTZ demonstrated significantly improved motor skills in a rotarod test compared to mice receiving vehicle. Thus, bioluminescent optogenetic stimulation of transplanted neuronal precursor cells shows promising effects in improving locomotor behavior in the aphakia PD mouse model and encourages further studies to elucidate the mechanisms and long-term outcomes of these beneficial effects. |
Databáze: | OpenAIRE |
Externí odkaz: |