Age-dependent visualization of neural progenitor cells within the rostral migratory stream via MRI and endogenously labeled micron-sized iron oxide particles

Abstract

The subventricular zone (SVZ) is one of the primary sources for rodent neural progenitor cells (NPC), however, aging greatly impacts the substructure of the region and rate of new cell birth. To determine if age impacts the rate of in vivo migration within animals, we examined the rostral migratory stream (RMS) of animals across 12 days using an established MRI technique. To visualize NPCs, we injected micron sized particles of iron oxide (MPIO) into the lateral ventricle to endogenously label cells within the SVZ, which then appeared as hypo-intensive spots within MR images. Our in vivo MRI data showed that the rate of migration was significantly different between all ages examined, with decreases in the distance traveled as age progressed. The total number of iron oxide labeled cells within the olfactory bulb on day 12, decrease significantly when compared across ages in ex vivo high-resolution scans. We also, for the first time, demonstrated the endogenous labeling of cells within the dentate gyrus (DG) of hippocampus. Here too, there was a significant decrease in the number of labeled cells within the structure across age. Histology of the NPCs verified the decrease in labeling of cells with doublecortin (DCX) as age progressed for both regions. The dramatic reduction of labeling in NPCs within the SVZ and DG observed with MRI, demonstrates the importance of understanding the impact of age on the relationship of NPC and disease.