scholarly journals In Vivo Targeted Magnetic Resonance Imaging of Endogenous Neural Stem Cells in the Adult Rodent Brain

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Xiao-Mei Zhong ◽  
Fang Zhang ◽  
Ming Yang ◽  
Xue-Hua Wen ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mr Imaging ◽  
Neural Stem Cells ◽  
Molecular Probe ◽  
Mammalian Brain ◽  
Intraventricular Administration ◽  
In Vivo Monitoring ◽  
Rodent Brain ◽  
Endogenous Neural Stem Cells

Neural stem cells in the adult mammalian brain have a significant level of neurogenesis plasticity. In vivo monitoring of adult endogenous NSCs would be of great benefit to the understanding of the neurogenesis plasticity under normal and pathological conditions. Here we show the feasibility of in vivo targeted MR imaging of endogenous NSCs in adult mouse brain by intraventricular delivery of monoclonal anti-CD15 antibody conjugated superparamagnetic iron oxide nanoparticles. After intraventricular administration of these nanoparticles, the subpopulation of NSCs in the anterior subventricular zone and the beginning of the rostral migratory stream could be in situ labeled and were in vivo visualized with 7.0-T MR imaging during a period from 1 day to 7 days after the injection. Histology confirmed that the injected targeted nanoparticles were specifically bound to CD15 positive cells and their surrounding extracellular matrix. Our results suggest that in vivo targeted MR imaging of endogenous neural stem cells in adult rodent brain could be achieved by using anti-CD15-SPIONs as the molecular probe; and this targeting imaging strategy has the advantage of a rapid in vivo monitoring of the subpopulation of endogenous NSCs in adult brains.

scholarly journals In Vivo Targeted MR Imaging of Endogenous Neural Stem Cells in Ischemic Stroke

Molecules ◽  
2016 ◽  
Vol 21 (9) ◽  
pp. 1143 ◽  
Author(s):  
Fang Zhang ◽  
Xiaohui Duan ◽  
Liejing Lu ◽  
Xiang Zhang ◽  
Xiaomei Zhong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ischemic Stroke ◽  
Mr Imaging ◽  
Neural Stem Cells ◽  
Endogenous Neural Stem Cells

scholarly journals In vitro and in vivo CRISPR-Cas9 screens reveal drivers of aging in neural stem cells of the brain

2021 ◽  
Author(s):  
Tyson J Ruetz ◽  
Chloe M Kashiwagi ◽  
Bhek Morton ◽  
Robin W Yeo ◽  
Dena S Leeman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Primary Cultures ◽  
Mammalian Brain ◽  
Aging Brain ◽  
Gene Knockouts ◽  
Old Mice

Aging impairs the ability of neural stem cells to transition from quiescence to activation (proliferation) in the adult mammalian brain. Neural stem cell (NSC) functional decline results in decreased production of new neurons and defective regeneration upon injury during aging, and this is exacerbated in Alzheimer's disease. Many genes are upregulated with age in NSCs, and the knockout of some of these boosts old NSC activation and rejuvenates aspects of old brain function. But systematic functional testing of genes in old NSCs - and more generally in old cells - has not been done. This has been a major limiting factor in identifying the most promising rejuvenation interventions. Here we develop in vitro and in vivo high-throughput CRISPR-Cas9 screening platforms to systematically uncover gene knockouts that boost NSC activation in old mice. Our genome-wide screening pipeline in primary cultures of young and old NSCs identifies over 300 gene knockouts that specifically restore old NSC activation. Interestingly, the top gene knockouts are involved in glucose import, cilium organization and ribonucleoprotein structures. To determine which gene knockouts have a rejuvenating effect for the aging brain, we establish a scalable CRISPR-Cas9 screening platform in vivo in old mice. Of the 50 gene knockouts we tested in vivo, 23 boost old NSC activation and production of new neurons in old brains. Notably, the knockout of Slc2a4, which encodes for the GLUT4 glucose transporter, is a top rejuvenating intervention for old NSCs. GLUT4 protein expression increases in the stem cell niche during aging, and we show that old NSCs indeed uptake ~2-fold more glucose than their young counterparts. Transient glucose starvation increases the ability of old NSCs to activate, which is not further improved by knockout of Slc2a4/GLUT4. Together, these results indicate that a shift in glucose uptake contributes to the decline in NSC activation with age, but that it can be reversed by genetic or external interventions. Importantly, our work provides scalable platforms to systematically identify genetic interventions that boost old NSC function, including in vivo in old brains, with important implications for regenerative and cognitive decline during aging.

scholarly journals Overexpression of cdk4 and cyclinD1 triggers greater expansion of neural stem cells in the adult mouse brain

2011 ◽  
Vol 208 (5) ◽  
pp. 937-948 ◽  
Author(s):  
Benedetta Artegiani ◽  
Dirk Lindemann ◽  
Federico Calegari
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Adult Neurogenesis ◽  
Adult Mouse ◽  
Physiological Role ◽  
Mammalian Brain ◽  
Temporal Control ◽  
Somatic Stem Cells

Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)–cyclinD1 complex in the adult mouse hippocampus cell-autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4–cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells.

scholarly journals DNA–gadolinium–gold nanoparticles for in vivo T1 MR imaging of transplanted human neural stem cells

Biomaterials ◽  
2016 ◽  
Vol 77 ◽  
pp. 291-306 ◽  
Author(s):  
Francesca J. Nicholls ◽  
Matthew W. Rotz ◽  
Harmanvir Ghuman ◽  
Keith W. MacRenaris ◽  
Thomas J. Meade ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gold Nanoparticles ◽  
Mr Imaging ◽  
Neural Stem Cells ◽  
Human Neural Stem Cells

scholarly journals A novel polymeric micelle used for in vivo MR imaging tracking of neural stem cells in acute ischemic stroke

RSC Advances ◽  
2017 ◽  
Vol 7 (25) ◽  
pp. 15041-15052 ◽  
Author(s):  
Liejing Lu ◽  
Yong Wang ◽  
Minghui Cao ◽  
Meiwei Chen ◽  
Bingling Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ischemic Stroke ◽  
Mr Imaging ◽  
Neural Stem Cells ◽  
Acute Ischemic Stroke ◽  
Cholic Acid ◽  
Polymeric Micelles ◽  
Polymeric Micelle ◽  
Biodegradable Poly

Novel cationic polymeric micelles based on biodegradable poly(aspartic acid-dimethylethanediamine)–lysine–cholic acid were synthesized for in vivo tracking therapeutic stem cells using MRI.

scholarly journals Strategies for Regenerating Striatal Neurons in the Adult Brain by Using Endogenous Neural Stem Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Kanako Nakaguchi ◽  
Hiroshi Masuda ◽  
Naoko Kaneko ◽  
Kazunobu Sawamoto
Keyword(s):  
Stem Cells ◽  
Ischemic Stroke ◽  
Neural Stem Cells ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Adult Brain ◽  
Neurological Deficits ◽  
Mammalian Brain ◽  
Striatal Neurons ◽  
Endogenous Neural Stem Cells

Currently, there is no effective treatment for the marked neuronal loss caused by neurodegenerative diseases, such as Huntington's disease (HD) or ischemic stroke. However, recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ) of the adult mammalian brain, including the human brain. Because some of these new neurons migrate to the injured striatum and differentiate into mature neurons, such new neurons may be able to replace degenerated neurons and improve or repair neurological deficits. To establish a neuroregenerative therapy using this endogenous system, endogenous regulatory mechanisms that can be co-opted for efficient regenerative interventions must be understood, along with any potential drawbacks. Here, we review current knowledge on the generation of new neurons in the adult brain and discuss their potential for use in replacing striatal neurons lost to neurodegenerative diseases, including HD, and to ischemic stroke.

In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2251-2261 ◽  
Author(s):  
C.M. Morshead ◽  
C.G. Craig ◽  
D. van der Kooy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Olfactory Bulb ◽  
Neural Stem Cells ◽  
Anterior Commissure ◽  
Mammalian Brain ◽  
Proliferating Cells ◽  
Asymmetric Mode ◽  
Clone Size

The adult mammalian forebrain contains a population of multipotential neural stem cells in the subependyma of the lateral ventricles whose progeny are the constitutively proliferating cells, which divide actively throughout life. The adult mammalian brain is ideal for examining the kinetics of the stem cells due to their strict spatial localization and the limited and discrete type of progeny generated (constitutively proliferating cells). Clonal lineage analyses 6 days after retrovirus infection revealed that under baseline conditions 60% of the constitutively proliferating cells undergo cell death, 25% migrate to the olfactory bulb and 15% remain confined to the lateral ventricle subependyma (where they reside for approximately 15 days). Analysis of single cell clones 31 days after retroviral infection revealed that the stem cell divides asymmetrically to self-renew and give rise to constitutively proliferating cells. Following repopulation of the depleted subependyma the average clone size is 2.8 times larger than control, yet the absolute number of cells migrating to the olfactory bulb is maintained and the stem cell retains its asymmetric mode of division. The number of neural stem cells in the adult forebrain 33 days after repopulation of the subependyma was estimated using bromodeoxyuridine labeling of subepenydmal cells. There were calculated to be 1200–1300 cells between the rostral corpus callosum and rostral anterior commissure; these data support a lineage model similar to those based on stem cell behavior in other tissue types.

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