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

Shuboni-Mulligan, Dorela; Chakravarty, Shatadru; Mallett, Christiane L.; Wolf, Anne; Dmitriev, Pauline; Forton, Stacey M.; Shapiro, Erik M.

doi:10.1016/j.neuroimage.2019.05.073

Cited by 7 publications

(8 citation statements)

References 40 publications

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“…Cell adhesion emerged as a hallmark of NSC aging in our study. The migratory properties of neuroblasts has started to be examined with age [44][45][46][47] and in the context of innervating distal tumors 73 . But the changes in migration and adhesion in quiescent and activated NSCs, the upstream NSC populations that give rise to migratory neuroblasts, remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Quiescent NSCs line the ventricles and can become activated (aNSCs) to give rise to neural progenitors (NPCs) and neuroblasts that migrate along the rostral migratory stream (RMS) to the olfactory bulb (OB) 10, 42,43 . While neuroblast migration has begun to be examined in older animals [44][45][46][47] , the adhesive and migratory properties of quiescent and activated NSCs and their progenitors in vivo during aging remain largely unstudied. As adhesion to the niche plays a key role in regulating NSC stemness and function 48 , we assessed quiescent and activated NSC localization in vivo by immunostaining of coronal brain sections from young and old individuals (Fig.…”

Section: Age-dependent Cell Adhesion and Migration Defects Of Quiescementioning

confidence: 99%

“…Neuroblasts then migrate long distances along the rostral migratory stream (RMS) to the olfactory bulb (OB) to give rise to new neurons (neurogenesis) 3,14,54 . While NSC/NPC and neuroblast migration has begun to be examined in older animals [55][56][57][58][59] , the adhesive and migratory properties of quiescent and activated NSCs (and their progenitors) has not been systematically studied in vivo during aging.…”

Section: Age-dependent Location Defects Of Quiescent and Activated Ns...mentioning

confidence: 99%

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Chromatin accessibility dynamics of neurogenic niche cells reveal defects in neural stem cell adhesion and migration during aging

Yeo

Zhou

Zhong

et al. 2021

Preprint

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Aging is accompanied by a deterioration in the regenerative and repair potential of stem cell regions in the brain. However, the mechanisms underlying this decline are largely unknown. Here we profile the chromatin landscape of five different cell types freshly isolated from the subventricular zone neurogenic niche of young and old mice. We find that chromatin states exhibit distinct changes with aging in different cell types. Notably, the chromatin of quiescent neural stem cells (NSCs) becomes more repressed with age whereas that of proliferative, activated NSCs becomes more open. Surprisingly, these opposing age-related chromatin changes involve cell adhesion and migration pathways. We experimentally validate that quiescent and activated NSCs exhibit opposite migratory deficits during aging. Quiescent NSCs become more migratory during aging, whereas activated NSCs and progeny become less migratory and less able to mobilize out of the niche in vivo during aging. The cellular mechanism by which aging impairs the migration of activated NSCs and progeny involves increased occurrence of force-producing focal adhesions. Inhibiting the cytoskeletal-regulating kinase ROCK in old activated NSCs and progenitors eliminates cell adhesive forces and boosts migration speed, reverting these cells to a more youthful migratory state. Our work has important implications for restoring the migratory potential of NSCs during aging and brain injury.

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Section: Discussionmentioning

confidence: 99%

Section: Age-dependent Cell Adhesion and Migration Defects Of Quiescementioning

confidence: 99%

Section: Age-dependent Location Defects Of Quiescent and Activated Ns...mentioning

confidence: 99%

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Chromatin accessibility dynamics of neurogenic niche cells reveal defects in neural stem cell adhesion and migration during aging

Yeo

Zhou

Zhong

et al. 2021

Preprint

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“…A series of aqueous solutions of nanocomposites (0−1 mM of Mn) were prepared and imaged on a 7 T BioSpec 70/30 USR (Bruker, MA) using a 9 cm diameter volume transmit coil and scanned with three across (0−0.2 and 0.3−0.5) and three coronal slices. The T 1 map is estimated with T 1 3000 ms. 40 2.10. Cellular Uptake Study.…”

Section: T H Imentioning

confidence: 99%

Biodegradable Hollow Manganese Silicate Nanocomposites to Alleviate Tumor Hypoxia toward Enhanced Photodynamic Therapy

Nafiujjaman

Chung

Kalashnikova

et al. 2020

ACS Appl. Bio Mater.

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Photodynamic therapy (PDT) has been extensively explored as a minimally invasive treatment strategy for malignant cancers. It works with the help of a photosensitizer located within cancer cells that is irradiated by near-infrared light to produce potent toxins and singlet oxygen ( 1 O 2 ) and induce cell death. However, reactive oxygen species can be overexpressed in tumor tissue because of the rapid metabolic activity in cancer cells, and the insufficient oxygenation (hypoxia) can lead to low production of singlet oxygen ( 1 O 2 ) during PDT. In this study, we developed nanocomposites composed of a hollow manganese silicate (HMnOSi) nanoparticle and a photosensitizer (Ce6) that can generate significant amounts of O 2 to relieve tumor hypoxia and enhance the therapeutic efficacy of PDT. Our nanocomposites were characterized by UV−vis, fluorescence spectroscopy, transmission electron microscopy (TEM), energy-dispersive X-ray, and dynamic light scattering. Our particles' hollow mesoporous structures were shown to retain large amounts of Ce6 on the particle surface with high loading capacity (33%). TEM imaging showed that the nanoparticles could be biodegradable over time in simulated body fluid, which can imply clinical potentials. Significant H 2 O 2 quenching capabilities to alleviate hypoxic conditions in a solid tumor were also presented. For breast cancer cells, the nanocomposite-treated group revealed that 91% of cells were dead under laser activation compared to 51% for the control group (free Ce6). In an animal study, our nanocomposites showed almost fourfold tumor growth inhibition versus the control and more than twofold over free Ce6 in orthotopic tumor xenografts. In addition, the oxygen saturation contrast inside tumors was evaluated by photoacoustic imaging to demonstrate the alleviated hypoxia in vivo. Our works provide a smart nanosystem to ameliorate the hypoxic tumor microenvironment and augment the efficacy of PDT in a targeted cancer treatment.

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“…Hippocampal neurogenesis rapidly declines with aging: By 9-12 months of age there is an 85-90% reduction in neurogenesis that is reduced even further by 20 months (Bondolfi et al, 2004;Ben Abdallah et al, 2010;Gil-Mohapel et al, 2013;Morel et al, 2015). Not only is neurogenesis declining, but neural progenitor cells also migrate much slower and much shorter distances as rodents age (Shuboni-Mulligan et al, 2019). Decreases in hippocampal neurogenesis due to aging likely contributes to age-related cognitive decline (Fischer et al, 1989;Gage et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Adolescent Binge-Type Ethanol Exposure in Rats Mirrors Age-Related Cognitive Decline by Suppressing Cholinergic Tone and Hippocampal Neurogenesis

Reitz

Nunes

Savage

2021

Front. Behav. Neurosci.

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Heavy alcohol consumption followed by periods of abstinence (i.e., binge drinking) during adolescence is a concern for both acute and chronic health issues. Persistent brain damage after adolescent intermittent ethanol exposure in rodents, a model of binge drinking, includes reduced hippocampal neurogenesis and a loss of neurons in the basal forebrain that express the cholinergic phenotype. The circuit formed between those regions, the septohippocampal pathway, is critical for learning and memory. Furthermore, this circuit is also altered during the aging process. Thus, we examined whether pathology in septohippocampal circuit and impairments in spatial behaviors are amplified during aging following adolescent intermittent ethanol exposure. Female and male rats were exposed to intermittent intragastric gavage of water (control) or 20% ethanol (dose of 5 g/kg) for a 2 days on/off cycle from postnatal days 25–55. Either 2 (young adult) or 12–14 (middle-age) months post exposure, rats were tested on two spatial tasks: spontaneous alternation and novel object in place. Acetylcholine efflux was assessed in the hippocampus during both tasks. There was no adolescent ethanol-induced deficit on spontaneous alternation, but middle-aged male rats displayed lower alternation rates. Male rats exposed to ethanol during adolescence had blunted behavioral evoked acetylcholine during spontaneous alternation testing. All ethanol-exposed rats displayed suppression of the cholinergic neuronal phenotype. On the novel object in place task, regardless of sex, ethanol-exposed rats performed significantly worse than control-treated rats, and middle aged-rats, regardless of sex or ethanol exposure, were significantly impaired relative to young adult rats. These results indicate that male rats display earlier age-related cognitive impairment on a working memory task. Furthermore, male rats exposed to ethanol during adolescence have blunted behavior-evoked hippocampal acetylcholine efflux. In addition, middle-aged and ethanol-exposed rats, regardless of sex, are impaired at determining discrete spatial relationship between objects. This type of pattern separation impairment was associated with a loss of neurogenesis. Thus, binge-type adolescent ethanol exposure does affect the septohippocampal circuit, and can accelerate age-related cognitive impairment on select spatial tasks.

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

Cited by 7 publications

References 40 publications

Chromatin accessibility dynamics of neurogenic niche cells reveal defects in neural stem cell adhesion and migration during aging

Chromatin accessibility dynamics of neurogenic niche cells reveal defects in neural stem cell adhesion and migration during aging

Biodegradable Hollow Manganese Silicate Nanocomposites to Alleviate Tumor Hypoxia toward Enhanced Photodynamic Therapy

Adolescent Binge-Type Ethanol Exposure in Rats Mirrors Age-Related Cognitive Decline by Suppressing Cholinergic Tone and Hippocampal Neurogenesis

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