Magnetic resonance imaging of odorant activity-dependent migration of neural precursor cells and olfactory bulb growth

Abstract

Neural progenitors or neuroblasts are produced by precursor cells in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) to the olfactory bulbs (OB) throughout life. In the OB, these adult born neurons either die or replace existing olfactory interneurons, playing a critical role in the stabilization of OB circuitry. Although several aspects of the addition of new neurons into the OB have been studied, it is unclear whether long-distance activity from the OB can regulate the influx of migrating neuroblasts along the RMS. In this study, iron oxide-assisted MRI was used to track the migration of neuroblasts in combination with reversible naris occlusion to manipulate odorant-induced activity. It was found that decreasing olfactory activity led to a decrease in the rate of neuroblast migration along the RMS. Removal of the naris occlusion led to an increase in migratory rate back to control levels, indicating that olfactory activity has regulatory function on neuroblast migration in the RMS. Blocking odorant activity also led to an arrest in OB growth and re-opening the block led to a rapid re-growth returning the bulb size to control levels. Furthermore, pharmacogenetic elimination of the neuroblasts demonstrated that they were required for re-growth of the bulb following sensory deprivation. Together, these results show that sensory activity, neural migration and OB growth are tightly coupled in an interdependent manner.

Tissue-Specific Ferritin- and GFP-Based Genetic Vectors Visualize Neurons by MRI in the Intact and Post-Ischemic Rat Brain

“…Currently, neuroinflammation can be assessed with MRI using injected ultrasmall superparamagnetic particles of iron oxide (SPIO) that are absorbed by macrophages [ 43 , 44 ]. It is known that inflammation-activated microglia and macrophages accumulate ferritin [ 40 ], which, in turn, can be visualized using T2* MRI [ 4 , 5 ]. Although the T2* technique is successfully used in the clinic for detecting iron accumulation in Parkinson’s disease [ 45 ], Alzheimer’s disease [ 45 ], multiple sclerosis [ 45 ], and hemorrhagic stroke [ 46 ], there are no data on application of T2* for imaging neuroinflammation in ischemic stroke in human patients.…”

“…Magnetic resonance imaging (MRI) is a highly-informative technique, which allows non-invasive visualization of anatomical structures and physiological processes, including neurogenesis, in the body [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Neurogenesis in pathological conditions is a complex process that evolves over time and includes migration of young neurons from neurogenic niches to the lesion site as well as formation of new neurogenic niches.…”

“…To distinguish specific cell populations in brain tissue, these cells must be labeled with MRI-detectable probes. A variety of superparamagnetic iron oxide particles (SPIOs) are used as MRI-contrasting agents for the injection into the lateral ventricles, or into the brain parenchyma near to the neurogenic subventricular zone (SVZ) [ 3 , 4 , 5 , 6 , 12 , 13 , 15 , 16 , 17 , 18 , 19 ]. The major drawback of this technique is that such agents create MRI-contrast regardless of whether they are absorbed by the cells or remain as free particles resided in the tissue [ 1 , 13 , 19 ].…”

Tracking Neural Progenitor Cell Migration in the Rodent Brain Using Magnetic Resonance Imaging

“…Nieman et al (2010) used image registration and intensity-based analysis to identify labeled cells and determine their speed of migration. They estimated that labeled NPCs move at 100–120 μm/h in the RMS and 50 μm/h in the OB (Nieman et al, 2010; Pothayee et al, 2017; Shuboni-Mulligan et al, 2018), slightly slower than the speeds of 150–700 μm/h that were measured in mice with tumors (Elvira et al, 2012). These migration rates are not far from those determined in studies of neurogenesis that employ immunohistochemical methods of detection, which determined a migration rate of 70–80 μm/h in naïve rodents (Nam et al, 2007).…”

“…These migration rates are not far from those determined in studies of neurogenesis that employ immunohistochemical methods of detection, which determined a migration rate of 70–80 μm/h in naïve rodents (Nam et al, 2007). Recently, the technique demonstrated that both environmental stimuli, olfactory activity (Pothayee et al, 2017) and aging (Shuboni-Mulligan et al, 2018) impacted migration rates in vivo . Understanding the dramatic decrease in NPC migration as animals aged is critical, as many diseases that recruit NPC are more prevalent in older individuals (Wang et al, 2013).…”