The spread of pathogenic proteins between cells in the mammalian nervous system has been documented in some neurodegenerative diseases. Researchers investigated the transfer of pathogenic and nonpathogenic cytosolic proteins between spinal cord motor neurons in chimeric mice.
To study whether mutant amyotrophic lateral sclerosis (ALS)-associated cytosolic SOD1 proteins spread between spinal cord motor neurons, the authors generated a chimeric mouse strain from donor ALS strains that expressed mutant SOD1 fused to two different fluorescent proteins.
At 3 months of age, the SOD1 chimeric mice exhibited extensive fluorescence from both proteins in individual spinal cord motor neurons and in ALS-affected cranial nerve motor nuclei. Next, the authors generated various nonpathogenic chimeric mouse strains, including a strain that incorporated a nonpathogenic cytosolic enhanced green fluorescent protein (EGFP) and the mitochondrial fluorescent protein mito-mCherry.
The authors found that this strain exhibited robust transfer of the EGFP protein to mito-mCherry neurons, suggesting that nonpathogenic cytosolic proteins might be capable of transfer between spinal cord neurons. Moreover, both the SOD1 and EGFP models exhibited fluorescence in oligodendrocytes, located near the motor neurons.
According to the authors, the findings suggest that oligodendrocytes might mediate protein transfer between motor neurons.
http://www.pnas.org/content/early/2017/03/23/1701465114
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