Effects of striatal transplantation of cells transfected with GDNF gene without pre- and pro-regions in mouse model of Parkinson’s disease
| Autor: | Galina Pavlova, Nadezda Kust, P. Teslia, N. Bazhenova, A. V. Revishchin, Dmitry Y. Panteleev, Vladimir M. Kovalzon, L. Moiseenko |
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| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Cell Transplantation animal diseases Striatum PC12 Cells chemistry.chemical_compound 0302 clinical medicine Glial cell line-derived neurotrophic factor biology General Neuroscience MPTP GDNF Cell biology Neurotrophin Research Article Tyrosine 3-Monooxygenase Green Fluorescent Proteins Neuronal Outgrowth Neurotrophic factor Substantia nigra Motor Activity Transfection 03 medical and health sciences Cellular and Molecular Neuroscience Parkinsonian Disorders Animals Humans Glial Cell Line-Derived Neurotrophic Factor Wakefulness Pars Compacta Tyrosine hydroxylase Pars compacta Dopaminergic Neurons Genetic Therapy Rats Transplantation Mice Inbred C57BL Neostriatum 030104 developmental biology HEK293 Cells chemistry nervous system Culture Media Conditioned Sleep-wakefulness cycle biology.protein Parkinson’s disease Sleep Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | BMC Neuroscience |
| ISSN: | 1471-2202 |
| DOI: | 10.1186/s12868-016-0271-x |
| Popis: | Background Previously, we have shown that transgenic cells bearing the GDNF gene with deleted pre- and pro-regions (mGDNF) can release transgenic GDNF. The medium conditioned by transgenic cells with mGDNF induced axonal growth in rat embryonic spinal ganglion in vitro. Here we demonstrate a neurotrophic effect of mGDNF on PC12 cells in vitro as well as its neuroprotective effect on dopaminergic neurons in the substantia nigra pars compacta in vivo as indicated by improved motor coordination and sleep-wakefulness cycle in the MPTP mouse model of Parkinson’s disease. Results HEK293 cells were transfected with a vector encoding an isoform of the human GDNF gene with deleted pre- and pro-regions (mGDNF). This factor in the medium conditioned by the transfected cells was shown to induce axonal growth in PC12 cells. The early Parkinson’s disease model was established by injection of the dopaminergic pro-neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into C57Bl/6 mice. Transgenic HEK293/mGDNF/GFP cells were transplanted into the striatum (caudate-putamen) of experimental mice. The sleep-wakefulness cycle was studied by continuous EEG and motor activity monitoring 1 and 2 weeks after MPTP injection. After the experiment, the motor coordination of experimental animals was evaluated in the rotarod test, and dopaminergic neurons in the substantia nigra pars compacta were counted in cross-sections of the midbrain. MPTP administration lowered the number of tyrosine hydroxylase immunopositive cells in the substantia nigra pars compacta, decreased motor coordination, and increased the total wake time during the dark period. The transplantation of HEK293/mGDNF cells into the caudate-putamen 3 days prior to MPTP injection smoothed these effects, while the control transplantation of HEK293 cells showed no notable impact. Conclusions Transplantation of transgenic cells with the GDNF gene lacking the pre- and pro-sequences can protect dopaminergic neurons in the mouse midbrain from the subsequent administration of the pro-neurotoxin MPTP, which is confirmed by polysomnographic, behavioral and histochemical data. Hence it is released from transfected cells and preserves the differentiation activity and neuroprotective properties. |
| Databáze: | OpenAIRE |
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