Depletion of neural stem cells from the subventricular zone of adult mouse brain using cytosine b‐Arabinofuranoside

Ghanbari, Amir; Esmaeilpour, Tahereh; Bahmanpour, Soghra; Golmohammadi, Mohammad Ghasem; Sharififar, Sharareh; Azari, Hassan

doi:10.1002/brb3.404

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…Taking together the overall dynamics of NSPCs in SVZ, RMS and OB, a mild reduction of Cu in the SVZ by the low-dose D-Pen treatment appeared to significantly increase newborn neurons in the OB, yet not at the cost of depleting the NSPC pool in the origin of SVZ. Since a depleted NSC pool, no matter partially or fully, can repopulate over a period of time [ 45 , 46 ], it would be interesting to investigate whether and how a prolonged D-Pen chelation may alter the NSC pool in the SVZ in our future experiments.…”

Section: Discussionmentioning

confidence: 99%

Copper Modulates Adult Neurogenesis in Brain Subventricular Zone

Liu

Rijn

Zheng

2022

IJMS

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The subventricular zone (SVZ) in lateral ventricles is the largest neurogenic region in adult brain containing high amounts of copper (Cu). This study aims to define the role of Cu in adult neurogenesis by chelating labile Cu ions using a well-established Cu chelator D-Penicillamine (D-Pen). A neurosphere model derived from adult mouse SVZ tissues was established and characterized for its functionality with regards to neural stem/progenitor cells (NSPCs). Applying D-Pen in cultured neurospheres significantly reduced intracellular Cu levels and reversed the Cu-induced suppression of NSPC’s differentiation and migration. An in vivo intracerebroventricular (ICV) infusion model was subsequently established to infuse D-Pen directly into the lateral ventricle. Metal analyses revealed a selective reduction of Cu in SVZ by 13.1% (p = 0.19) and 21.4% (p < 0.05) following D-Pen infusions at low (0.075 μg/h) and high (0.75 μg/h) doses for 28 days, respectively, compared to saline-infused controls. Immunohistochemical studies revealed that the 7-day, low-dose D-Pen infusion significantly increased Ki67(+)/Nestin(+) cell counts in SVZ by 28% (p < 0.05). Quantification of BrdU(+)/doublecortin (DCX)(+) newborn neuroblasts in the rostral migration stream (RMS) and olfactory bulb (OB) further revealed that the short-term, low-dose D-Pen infusion, as compared with saline-infused controls, resulted in more newborn neuroblasts in OB, while the high-dose D-Pen infusion showed fewer newborn neuroblasts in OB but with more arrested in the RMS. Long-term (28-day) infusion revealed similar outcomes. The qPCR data from neurosphere experiments revealed altered expressions of mRNAs encoding key proteins known to regulate SVZ adult neurogenesis, including, but not limited to, Shh, Dlx2, and Slit1, in response to the changed Cu level in neurospheres. Further immunohistochemical data indicated that Cu chelation also altered the expression of high-affinity copper uptake protein 1 (CTR1) and metallothionein-3 (MT3) in the SVZ as well as CTR1 in the choroid plexus, a tissue regulating brain Cu homeostasis. Taken together, this study provides first-hand evidence that a high Cu level in SVZ appears likely to maintain the stability of adult neurogenesis in this neurogenic zone.

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Section: Discussionmentioning

confidence: 99%

Copper Modulates Adult Neurogenesis in Brain Subventricular Zone

Liu

Rijn

Zheng

2022

IJMS

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“…Depending on the cell type, in vitro maturity may be attained over several weeks and can be facilitated by specialized reagents (e.g., BrainPhys medium) to accelerate synapse formation and the emergence of electrophysiological activity that may better reflect properties of postmitotic neurons in vivo ( 126 , 127 ). Mitotic inhibitors such as cytosine arabinoside (AraC) ( 128 ) and uridine/fluorodeoxyuridine (U/FdU) ( 129 ) can synchronize maturation by eliminating NPCs from the network, especially when the inhibitors are infused intermittently to account for quiescent NPCs working to repopulate depleted progeny ( 128 ). Although these methods allow for some degree of control over the initiation of differentiation, there are still many outstanding questions as to how to define cellular maturity and the most salient features may depend on the experimental question.…”

Section: Two-dimensional Culturesmentioning

confidence: 99%

Using 2D and 3D pluripotent stem cell models to study neurotropic viruses

2022

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Understanding the impact of viral pathogens on the human central nervous system (CNS) has been challenging due to the lack of viable human CNS models for controlled experiments to determine the causal factors underlying pathogenesis. Human embryonic stem cells (ESCs) and, more recently, cellular reprogramming of adult somatic cells to generate human induced pluripotent stem cells (iPSCs) provide opportunities for directed differentiation to neural cells that can be used to evaluate the impact of known and emerging viruses on neural cell types. Pluripotent stem cells (PSCs) can be induced to neural lineages in either two- (2D) or three-dimensional (3D) cultures, each bearing distinct advantages and limitations for modeling viral pathogenesis and evaluating effective therapeutics. Here we review the current state of technology in stem cell-based modeling of the CNS and how these models can be used to determine viral tropism and identify cellular phenotypes to investigate virus-host interactions and facilitate drug screening. We focus on several viruses (e.g., human immunodeficiency virus (HIV), herpes simplex virus (HSV), Zika virus (ZIKV), human cytomegalovirus (HCMV), SARS-CoV-2, West Nile virus (WNV)) to illustrate key advantages, as well as challenges, of PSC-based models. We also discuss how human PSC-based models can be used to evaluate the safety and efficacy of therapeutic drugs by generating data that are complementary to existing preclinical models. Ultimately, these efforts could facilitate the movement towards personalized medicine and provide patients and physicians with an additional source of information to consider when evaluating available treatment strategies.

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“…SVZ, the largest neurogenic region in the brain is extended from the olfactory bulb to the crossing of the anterior commissure. The existing neural progenitor cells generate neurons, astrocytes and oligodendrocytes in vitro [2][3][4] . NSCs reside in a vascular microenvironment that…”

Section: Neural Stem Cellsmentioning

confidence: 99%

An Experimental Investigation of Ultraweak Photon Emission from Adult Murine Neural Stem Cells

Esmaeilpour

Fereydouni

Dehghani

et al. 2020

Sci Rep

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neurons like other living cells may have ultraweak photon emission (Upe) during neuronal activity. this study is aimed to evaluate Upe from neural stem cells (nSc) during their serial passaging and differentiation. We also investigate whether the addition of silver nanoparticles (AgNPs) or enhancement of UPE (by AgNPs or mirror) affect the differentiation of NSC. In our method, neural stem and progenitor cells of subventricular zone (SVZ) are isolated and expanded using the neurosphere assay. the obtained dissociated cells allocated and cultivated into three groups: groups: i: cell (control), ii: cell + mirror, and iii: cell + Agnps. After seven days, the primary neurospheres were counted and their mean number was obtained. Serial passages continuous up to sixth passages in the control group. Differentiation capacity of the resulting neurospheres were evaluated in vitro by immunocytochemistry techniques. Measurement of Upe was carried out by photomultiplier tube (pMt) in the following steps: at the end of primary culture, six serial cell passages of the control group, before and after of the differentiation for 5 minutes. The results show that neither mirror nor AgNPs affect on the neurosphere number. The UPE of the NSC in the sixth subculturing passage was significantly higher than in the primary passage (P < 0.05). AgNPs significantly increased the UPE of the NSC compared to the control group before and after the differentiation (P < 0.05). Also, the treatment with AgNPs increased 44% neuronal differentiation of the harvested NSCs. UPE of NSC after the differentiation was significantly lower than that before the differentiation in each groups, which is in appropriate to the cell numbers (P < 0.0001). The mirror did not significantly increase UPE, neither before nor after the differentiation of nSc. As a conclusion, nSc have Upe-properties and the intensity is increased by serial passaging that are significant in the sixth passage. The AgNPs increases the UPE intensity of NSC that pushes more differentiation of NSC to the neurons. The mirror was not effective in enhancement of UPE. As a result, UPE measurement may be suitable for assessing and studying the effects of nanoparticles in living cells and neurons.

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Depletion of neural stem cells from the subventricular zone of adult mouse brain using cytosine b‐Arabinofuranoside

Cited by 6 publications

References 24 publications

Copper Modulates Adult Neurogenesis in Brain Subventricular Zone

Copper Modulates Adult Neurogenesis in Brain Subventricular Zone

Using 2D and 3D pluripotent stem cell models to study neurotropic viruses

An Experimental Investigation of Ultraweak Photon Emission from Adult Murine Neural Stem Cells

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