scholarly journals A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells

2019 ◽  
Vol 5 (2) ◽  
pp. eaav4416 ◽  
Author(s):  
Jian Dong ◽  
Yuan-Bo Pan ◽  
Xin-Rong Wu ◽  
Li-Na He ◽  
Xian-Dong Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Granule Cells ◽  
Adult Brain ◽  
Cell Contact ◽  
External Signal ◽  
Neurogenic Niche ◽  
Functional Transition ◽  
Newborn Neurons ◽  
Cell Cell

The quiescence of radial neural stem cells (rNSCs) in adult brain is regulated by environmental stimuli. However, little is known about how the neurogenic niche couples the external signal to regulate activation and transition of quiescent rNSCs. Here, we reveal that long-term excitation of hippocampal dentate granule cells (GCs) upon voluntary running leads to activation of adult rNSCs in the subgranular zone and thereby generation of newborn neurons. Unexpectedly, the role of these excited GC neurons in NSCs depends on direct GC-rNSC interaction in the local niche, which is through down-regulated ephrin-B3, a GC membrane–bound ligand, and attenuated transcellular EphB2 kinase–dependent signaling in the adjacent rNSCs. Furthermore, constitutively active EphB2 kinase sustains the quiescence of rNSCs during running. These findings thus elucidate the physiological significance of GC excitability on adult rNSCs under external environments and indicate a key-lock switch regulation via cell-cell contact for functional transition of rNSCs.

Adult Neurogenesis: Lessons from Crayfish and the Elephant in the Room

2016 ◽  
Vol 87 (3) ◽  
pp. 146-155 ◽  
Author(s):  
Barbara S. Beltz ◽  
Georg Brenneis ◽  
Jeanne L. Benton
Keyword(s):  
Stem Cells ◽  
Immune System ◽  
Neural Stem Cells ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Neural Precursor ◽  
Neural Precursors ◽  
Neurogenic Niche ◽  
Fetal Microchimerism ◽  
The Brain

The 1st-generation neural precursors in the crustacean brain are functionally analogous to neural stem cells in mammals. Their slow cycling, migration of their progeny, and differentiation of their descendants into neurons over several weeks are features of the neural precursor lineage in crayfish that also characterize adult neurogenesis in mammals. However, the 1st-generation precursors in crayfish do not self-renew, contrasting with conventional wisdom that proposes the long-term self-renewal of adult neural stem cells. Nevertheless, the crayfish neurogenic niche, which contains a total of 200-300 cells, is never exhausted and neurons continue to be produced in the brain throughout the animal's life. The pool of neural precursors in the niche therefore cannot be a closed system, and must be replenished from an extrinsic source. Our in vitro and in vivo data show that cells originating in the innate immune system (but not other cell types) are attracted to and incorporated into the neurogenic niche, and that they express a niche-specific marker, glutamine synthetase. Further, labeled hemocytes that undergo adoptive transfer to recipient crayfish generate cells in neuronal clusters in the olfactory pathway of the adult brain. These hemocyte descendants express appropriate neurotransmitters and project to target areas typical of neurons in these regions. These studies indicate that under natural conditions, the immune system provides neural precursors supporting adult neurogenesis in the crayfish brain, challenging the canonical view that ectodermal tissues generating the embryonic nervous system are the sole source of neurons in the adult brain. However, these are not the first studies that directly implicate the immune system as a source of neural precursor cells. Several types of data in mammals, including adoptive transfers of bone marrow or stem cells as well as the presence of fetal microchimerism, suggest that there must be a population of cells that are able to access the brain and generate new neurons in these species.

scholarly journals Intermediate progenitors support migration of neural stem cells into dentate gyrus outer neurogenic niches

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Branden R Nelson ◽  
Rebecca D Hodge ◽  
Ray AM Daza ◽  
Prem Prakash Tripathi ◽  
Sebastian J Arnold ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Dentate Gyrus ◽  
Lineage Tracing ◽  
Cell Contact ◽  
Genetic Lineage ◽  
Multiphoton Imaging ◽  
Intermediate Progenitors ◽  
Dynamic Cell ◽  
Cell Cell

The hippocampal dentate gyrus (DG) is a unique brain region maintaining neural stem cells (NCSs) and neurogenesis into adulthood. We used multiphoton imaging to visualize genetically defined progenitor subpopulations in live slices across key stages of mouse DG development, testing decades old static models of DG formation with molecular identification, genetic-lineage tracing, and mutant analyses. We found novel progenitor migrations, timings, dynamic cell-cell interactions, signaling activities, and routes underlie mosaic DG formation. Intermediate progenitors (IPs, Tbr2+) pioneered migrations, supporting and guiding later emigrating NSCs (Sox9+) through multiple transient zones prior to converging at the nascent outer adult niche in a dynamic settling process, generating all prenatal and postnatal granule neurons in defined spatiotemporal order. IPs (Dll1+) extensively targeted contacts to mitotic NSCs (Notch active), revealing a substrate for cell-cell contact support during migrations, a developmental feature maintained in adults. Mouse DG formation shares conserved features of human neocortical expansion.

scholarly journals Direct cell–cell contact with the vascular niche maintains quiescent neural stem cells

2014 ◽  
Vol 16 (11) ◽  
pp. 1045-1056 ◽  
Author(s):  
Cristina Ottone ◽  
Benjamin Krusche ◽  
Ariadne Whitby ◽  
Melanie Clements ◽  
Giorgia Quadrato ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Contact ◽  
Vascular Niche ◽  
Direct Cell ◽  
Cell Cell

Effect of temozolomide on neurogenesis and anxiety in the adult mouse brain.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23082-e23082
Author(s):  
Syed Hussaini ◽  
Mihyeon Jang
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cellular Proliferation ◽  
Radial Glia ◽  
Malignant Gliomas ◽  
Brain Slices ◽  
Adult Brain ◽  
Neuronal Maturation ◽  
Dividing Cells ◽  
Newborn Neurons

e23082 Background: The hippocampus is one of two regions in the adult brain where new neurons are generated well into adulthood. Newborn neurons develop from neural stem cells, and are consequently integrated into the hippocampal circuitry to function in learning and memory. Temozolomide (TMZ) is a commonly used alkylating agent for treatment of malignant gliomas. In this study, we examine the effects of TMZ on adult neurogenesis and cognitive function in the murine model. Methods: Adult male mice (8-week-old) were injected daily with TMZ (25 mg/kg, i.p.) for 2, 2.5 and 3.5 weeks to estimate progenitor proliferation, neuronal maturation and animal behavior respectively. For progenitor proliferation, a single dose of BrdU (50mg/kg, i.p.) was injected at 2 weeks and the mice sacrificed 2 hours later. For maturation analysis, five separate doses of EdU (41.1 mg/kg, i.p.) were injected over five days starting at 2 weeks. Three weeks after first EdU injection mice were sacrificed. Both BrdU and EdU are novel thymidine analogues that label dividing cells. Immunostaining was performed on hippocampal brain slices to label progenitors at different stages of development. For behavioral analysis, daily tests measuring anxiety, memory and motor activity were started at 2 weeks into TMZ administration. Results: TMZ significantly reduced the resident radial glia-like and non-radial glia-like population (MCM2+Nestin+), as well as the overall proliferating progenitor pool (n = 2, p < 0.05). In addition, it significantly reduced the population of Type-3 neuroblasts (EdU+DCX+NeuN-) (n = 4, p < 0.05). During neuronal maturation, immature new neurons (EdU+DCX+NeuN+) and mature new neurons (EdU+DCX-NeuN+) were also reduced by TMZ (n = 4, p < 0.05). These effects of TMZ coincided with specific behavioral deficits. While TMZ had no effect on working memory and locomotor activity, mice that underwent TMZ administration showed significantly increased anxiety on the open field test (n = 7, p < 0.05). Conclusions: Our findings demonstrate TMZ significantly impairs cellular proliferation of neural stem cells and fate-committed neuroblasts, and increases anxiety with sparing of non-hippocampal-dependent memory. TMZ may thus be associated with specific deficits in hippocampal function in the adult brain, providing mechanistic insight into adverse effects that may be observed with TMZ treatment.

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