scholarly journals Stereological characterization of neurogenic niche secretory cell types in the mouse dorsal dentate gyrus

2019 ◽  
Author(s):  
Joshua D. Rieskamp ◽  
Patricia Sarchet ◽  
Bryon M. Smith ◽  
Elizabeth D. Kirby

AbstractAdult neurogenesis in the dorsal dentate gyrus (DG) subregion of the mammalian hippocampus supports critical cognitive processes related to memory. Local DG cell populations form a neurogenic niche specialized to regulate adult neurogenesis. Recently, DG astrocytes, microglia, endothelia, and neural stem cells have been identified as sources of neurogenesismodulating secreted factors. Accurately estimating the size of these cell populations is useful for elucidating their relative contributions to niche physiology. Previous studies have characterized these cell types individually, but to our knowledge no comprehensive study of all these cell types exists. This is problematic because considerable variability in reported population size complicates comparisons across studies. Here, we apply consistent stereological methods within a single study to estimate cell density for neurogenesis-modulating secretory cell types in the dorsal DG of adult mice. We used immunohistochemical phenotypic markers to quantify cell density and found that stellate astrocytes were the most numerous followed by endothelia, intermediate progenitors, microglia, and neural stem cells. We did not observe any significant sex differences in cell density. We expect our data will facilitate efforts to elucidate the role of DG secretory cell populations in regulating adult neurogenesis.

2016 ◽  
Vol 87 (3) ◽  
pp. 146-155 ◽  
Author(s):  
Barbara S. Beltz ◽  
Georg Brenneis ◽  
Jeanne L. Benton

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.


2021 ◽  
Vol 7 (21) ◽  
pp. eabf5606
Author(s):  
Mohammad Shariq ◽  
Vinaya Sahasrabuddhe ◽  
Sreevatsan Krishna ◽  
Swathi Radha ◽  
Nruthyathi ◽  
...  

Inflammation is known to adversely affect adult neurogenesis, wherein the source of inflammation is largely thought to be extraneous to the neurogenic niche. Here, we demonstrate that the adult hippocampal neural progenitors harbor an inflammatory potential that is proactively suppressed by transcription factor 4 (Tcf4). Deletion of Tcf4 in hippocampal nestin-expressing progenitors causes loss of proliferative capacity and acquisition of myeloid inflammatory properties. This transformation abolishes their differentiation potential and causes production of detrimental factors that adversely affect niche cells, causing inflammation in the dentate gyrus. Thus, on one hand, Tcf4 deletion causes abrogation of proliferative progenitors leading to reduction of adult neurogenesis, while on the other, their accompanying inflammatory transformation inflicts inflammation in the niche. Taken together, we provide the first evidence for a latent inflammatory potential of adult hippocampal neural progenitors and identify Tcf4 as a critical regulator that facilitates adult neurogenesis via proactive suppression of this detrimental potential.


STEMedicine ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. e19
Author(s):  
Jelena Ban ◽  
Miranda Mladinic

Neural stem cells are capable of generating new neurons during development as well as in the adulthood and represent one of the most promising tools to replace lost or damaged neurons after injury or neurodegenerative disease. Unlike the brain, neurogenesis in the adult spinal cord is poorly explored and the comprehensive characterization of the cells that constitute stem cell neurogenic niche is still missing. Moreover, the terminology used to specify developmental and/or anatomical CNS regions, where neurogenesis in the spinal cord occurs, is not consensual and the analogy with the brain is often unclear. In this review, we will try to describe the heterogeneity of the stem cell types in the spinal cord ependymal zone, based on their origin and stem cell potential. We will also consider specific animal in vitro models that could be useful to identify “the right” stem cell candidate for cell replacement therapies.   


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1468
Author(s):  
Yashika S. Kamte ◽  
Manisha N. Chandwani ◽  
Alexa C. Michaels ◽  
Lauren A. O’Donnell

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.


2008 ◽  
Vol 363 (1500) ◽  
pp. 2111-2122 ◽  
Author(s):  
Hideyuki Okano ◽  
Kazunobu Sawamoto

Recent advances in stem cell research, including the selective expansion of neural stem cells (NSCs) in vitro , the induction of particular neural cells from embryonic stem cells in vitro , the identification of NSCs or NSC-like cells in the adult brain and the detection of neurogenesis in the adult brain (adult neurogenesis), have laid the groundwork for the development of novel therapies aimed at inducing regeneration in the damaged central nervous system (CNS). There are two major strategies for inducing regeneration in the damaged CNS: (i) activation of the endogenous regenerative capacity and (ii) cell transplantation therapy. In this review, we summarize the recent findings from our group and others on NSCs, with respect to their role in insult-induced neurogenesis (activation of adult NSCs, proliferation of transit-amplifying cells, migration of neuroblasts and survival and maturation of the newborn neurons), and implications for therapeutic interventions, together with tactics for using cell transplantation therapy to treat the damaged CNS.


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