Dataset Information

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

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.

SUBMITTER: Shuboni-Mulligan DD

PROVIDER: S-EPMC6688911 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Shuboni-Mulligan Dorela D DD Chakravarty Shatadru S Mallett Christiane L CL Wolf Alexander M AM Dmitriev Pauline M PM Forton Stacey M SM Shapiro Erik M EM

NeuroImage 20190529

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 t ...[more]

PMID: 31152841

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Project description:Recent efforts in biomaterial-assisted brain tissue engineering suggest that match of mechanical properties of biomaterials to those of native brain tissue may be crucial for brain regeneration. In particular, the mechanical properties of native brain tissue vary as a function of age. To date, detailed characterization of age-dependent viscoelastic properties of brain tissue throughout the postnatal development to adulthood is only available at sparse age points in animal studies. To fill this gap, we have characterized the linear viscoelastic properties of the cerebral cortex in rats at well-spaced ages from postnatal day 4 to 4 months old, the age range that is widely used in neural regeneration studies. Using an oscillatory rheometer, the viscoelastic properties of rat cortical slices were measured independently by storage moduli (G') and loss moduli (G″). The data demonstrated increases in both the storage moduli and the loss moduli of cortex tissue over post-natal age in rats. At all ages, the damping factor (G″/G' ratio) remained constant at low oscillatory strain frequencies (<10 rad/s) before it started to decline at medium frequency range (10-100 rad/s). Such changes were not age-dependent. The stress-relaxation response increased over post-natal age, consistent with the increasing tissue stiffness. Taken together, our study demonstrates that age is a crucial factor determining the mechanical properties of the cerebral cortex in rats during early postnatal development. This data may provide the guidelines for age-specific biomechanics study of brain tissue and help to define the mechanical properties of biomaterials for biomaterial-assisted brain tissue regeneration studies.Statement of significanceStudies about age-dependent viscoelastic properties of rat brain tissue throughout the postnatal development to adulthood is sparsely available. To fill up the gap of knowledge, in this study, we have characterized the age-dependent viscoelastic properties and the linear viscoelastic properties of the cerebral cortex throughout the postnatal development stage to adulthood in rats by measuring storage moduli (G'), loss moduli (G″), damping factor (G″/G' ratio) and stress-relaxation response. We have found that age is a crucial factor determining the mechanical properties of the cerebral cortex in rats during early postnatal development. The findings of this study could provide guidelines for age-specific biomechanical study of brain tissue and help to define the mechanical properties of biomaterials for biomaterial-assisted brain tissue regeneration in experimental models in rats.

Dataset Information

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

Publications

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

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