NDLI: Optimized Quantities of GDNF Overexpressed by Engineered Astrocytes Are Critical for Protection of Neuroblastoma Cells Against 6-OHDA Toxicity

Content Provider	Springer Nature Link
Author	Safi, Roya Gardaneh, Mossa Panahi, Yasin Maghsoudi, Nader Zaefizadeh, Mohammad Gharib, Ehsan
Copyright Year	2011
Abstract	Optimized levels of glial cell line-derived neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) are critical for protection of dopaminergic neurons against parkinsonian cell death. Recombinant lentiviruses harboring GDNF coding sequence were constructed and used to infect astrocytoma cell line 1321N1. The infected astrocytes overexpressed GDNF mRNA and secreted an average of 2.2 ng/mL recombinant protein as tested in both 2 and 16 weeks post-infection. Serial dilutions of GDNF-enriched conditioned medium from infected astrocytes added to growing neuroblastoma cell line SK-N-MC resulted in commensurate resistance against 6-OHDA toxicity. SK-N-MC cell survival rate rose from 51% in control group to 84% in the cells grown with astro-CM containing 453 pg secreted GDNF, an increase that was highly significant (P < 0.0001). However, larger volumes of the GDNF-enriched conditioned medium failed to improve cell survival and addition of volumes that contained 1,600 pg or more GDNF further reduced survival rate to below 70%. Changes in cell survival paralleled to changes in the percent of apoptotic cell morphologies. These data demonstrate the feasibility of using astrocytes as minipumps to stably oversecrete neurotrophic factors and further indicate that GDNF can be applied to neuroprotection studies in PD pending the optimization of its concentrations.
Starting Page	654
Ending Page	665
Page Count	12
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	46
Issue Number	3
e-ISSN	15591166
Language	English
Publisher	Humana Press Inc
Publisher Date	2011-10-04
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	GDNF Dopaminergic Astrocytes Neuroprotection Lentivirus Lentiviral vectors Parkinson's disease Neurology Cell Biology Neurochemistry Proteomics Neurosciences
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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