In vivo serial MRI of age-dependent neural progenitor cell migration in the rat brain

Dorela D Shuboni-Mulligan; Shatadru Chakravarty; Christiane L Mallett; Alexander M Wolf; Pauline M Dmitriev; Stacey M Forton; Erik M Shapiro

doi:10.1016/j.neuroimage.2019.05.073

In vivo serial MRI of age-dependent neural progenitor cell migration in the rat brain

Neuroimage. 2019 Oct 1:199:153-159. doi: 10.1016/j.neuroimage.2019.05.073. Epub 2019 May 29.

Authors

Dorela D Shuboni-Mulligan¹, Shatadru Chakravarty², Christiane L Mallett², Alexander M Wolf¹, Pauline M Dmitriev³, Stacey M Forton¹, Erik M Shapiro⁴

Affiliations

¹ Department of Radiology, Michigan State University, East Lansing, MI, USA.
² Department of Radiology, Michigan State University, East Lansing, MI, USA; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
³ School of Medicine, Duke University, Durham, NC, USA.
⁴ Department of Radiology, Michigan State University, East Lansing, MI, USA; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA. Electronic address: shapir86@msu.edu.

Abstract

The subventricular zone (SVZ) is a neurogenic niche in the mammalian brain, giving rise to migratory neural progenitor cells (NPC). In rodents, it is well-established that neurogenesis decreases with aging. MRI-based cell tracking has been used to measure various aspects of neurogenesis and NPC migration in rodents, yet it has not yet been validated in the context of age-related decrease in neurogenesis. This validation is critical to using these MRI techniques to study changes in neurogenesis that arise in diseases prevalent in aging populations and their combination with advanced cellular therapeutic approaches aiming to combat neurodegeneration. As such, in this work we used MRI-based cell tracking to measure endogenous neurogenesis and cell migration from the SVZ along the rostral migratory stream to the olfactory bulb, for 12 days duration, in rats aged 9 weeks to 2 years old. To enable the specific detection of NPCs by MRI, we injected micron sized particles of iron oxide (MPIOs) into the lateral ventricle to endogenously label cells within the SVZ, which then appeared as hypo-intensive spots within MR images. In vivo MRI data showed that the rate of NPC migration was significantly different between all ages examined, with decreases in the distance traveled and migration rate as age progressed. The total number of MPIO-labeled cells within the olfactory bulb on day 12, was significantly decreased when compared across ages in ex vivo high-resolution scans. We also demonstrate for the first-time, provocative preliminary data suggesting age-dependent MPIO uptake within the dentate gyrus (DG) as well. Histology to identify doublecortin-positive NPCs, verified the decrease in cell labeling as a function of aging, for both regions. The dramatic reduction of NPC labeling within the SVZ observed with MRI, validates the sensitivity of MRI-based cell tracking to neurogenic potential and demonstrates the importance of understanding the impact of age on the relationship of NPC and disease.

Keywords: Aging; Cell tracking; Iron oxide; Rostral migratory stream; Stem cells.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Aging*
Animals
Cell Movement / physiology
Cell Tracking / methods*
Dentate Gyrus / diagnostic imaging*
Doublecortin Protein
Ferric Compounds
Lateral Ventricles / diagnostic imaging*
Magnetic Resonance Imaging / methods*
Neural Stem Cells / physiology*
Rats
Rats, Inbred F344
Staining and Labeling

Substances

Dcx protein, rat
Doublecortin Protein
Ferric Compounds
ferric oxide

Abstract

Publication types

MeSH terms

Substances

Grants and funding