scholarly journals Greater Number of Microglia in Telencephalic Proliferative Zones of Human and Non-Human Primate Compared to Other Vertebrate Species

Author(s):  
Elisa Penna ◽  
Christopher L Cunningham ◽  
Stephanie Saylor ◽  
Anna Kreutz ◽  
Alice F Tarantal ◽  
...  

Abstract Microglial cells, the innate immune cells of the brain, are derived from yolk sac precursor cells, begin to colonize the telencephalon at the onset of cortical neurogenesis, and occupy specific layers including the telencephalic proliferative zones. Microglia are an intrinsic component of cortical germinal zones, establish extensive contacts with neural precursor cells (NPCs) and developing cortical vessels, and regulate the size of the NPC pool through mechanisms that include phagocytosis. Microglia exhibit notable differences in number and distribution in the prenatal neocortex between rat and Old World nonhuman primate telencephalon, suggesting that microglia exhibit distinct properties across vertebrate species. To begin addressing this subject we quantified the number of microglia and NPCs in proliferative zones of the fetal human, rhesus monkey, ferret, and rat, and the pre-hatch chick and turtle telencephalon. We show that the ratio of NPCs to microglia varies significantly across species. Few microglia populate the pre-hatch chick telencephalon, but the number of microglia approaches that of NPCs in fetal human and non-human primate telencephalon. These data demonstrate that microglia are in a position to perform similar functions in a number of vertebrate species, but more heavily colonize proliferative zones of fetal human and rhesus monkey telencephalon.

Stem Cells ◽  
2008 ◽  
Vol 26 (7) ◽  
pp. 1673-1682 ◽  
Author(s):  
Christine Rampon ◽  
Nicolas Weiss ◽  
Cyrille Deboux ◽  
Nathalie Chaverot ◽  
Florence Miller ◽  
...  

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi127-vi127
Author(s):  
Adam Grippin ◽  
Brandon Wummer ◽  
Hector Mendez-Gomez ◽  
Brian Stover ◽  
Jianping Huang ◽  
...  

Abstract BACKGROUND While dendritic cell (DC) vaccine therapy has shown considerable promise for glioblastoma (GBM) patients (Mitchell et al. Nature, 2015), their advancement into human clinical trials has been fraught with challenges in the development, manufacturing, and marketing of successful cancer immunotherapies. To circumvent the challenges associated with cell therapy, we have developed a new platform technology consisting of tumor derived mRNA complexed into lipid-nanoparticles (RNA-NPs) for systemic delivery to DCs in vivo and induction of antigen specific T cell immunity against GBM. OBJECTIVES/ METHODS We sought to assess if surface and charge modifications to our custom lipid-NP could facilitate its localization to lymphoid organs and the brain tumor microenvironment. RESULTS We demonstrate that intravenous administration of our unmodified custom RNA-NPs mediate systemic activation of DCs; these include activation of CD11c+ cells in the brains of animals with intact blood brain-barriers (BBBs). RNA-NPs mediate antigen specific T cell immunity and anti-tumor efficacy with increased tumor infiltrating lymphocytes against a NF-1/p53 mutant glioma that recapitulates features of human GBM in immunocompetent mice. Modification of surface charge could direct these RNA-NPs to lymphoid organs (e.g. spleen, lymph nodes) while modification of the lipid backbone (with cholesterol) enhances localization to innate immune cells in NF-1/p53 mutant and GL261 gliomas. We therefore assessed if this customizable lipid-NP could be leveraged for delivery of immune checkpoint inhibitors (ICIs) (i.e. PD-L1 siRNA) to the brain tumor microenvironment. Compared with scrambled siRNA-NPs in combination with ICIs, surface modified siRNA-NPs (antagonizing PD-L1) in combination with ICIs mediated significant antitumor efficacy with 37% long term survivors in an otherwise fatal brain tumor model. CONCLUSION We designed multifunctional RNA-NPs with a simple, scalable synthesis method that enables delivery of nucleic acids to innate immune cells in lymphoid organs and brain tumors.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Jiao ◽  
Björn Palmgren ◽  
Ekaterina Novozhilova ◽  
Ulrica Englund Johansson ◽  
Anne L. Spieles-Engemann ◽  
...  

Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation.Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application ofβ-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact.Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus.Conclusion. Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN).


2018 ◽  
Vol 78 (4) ◽  
pp. 374-390
Author(s):  
Keiu Kask ◽  
Laura Tikker ◽  
Katrin Ruisu ◽  
Sirje Lulla ◽  
Eva-Maria Oja ◽  
...  

2010 ◽  
Vol 7 (1) ◽  
pp. 62 ◽  
Author(s):  
Kristian P Doyle ◽  
Egle Cekanaviciute ◽  
Lauren E Mamer ◽  
Marion S Buckwalter

Toxicology ◽  
2021 ◽  
pp. 152922
Author(s):  
Daiane Cattani ◽  
Nona Struyf ◽  
Vivien Steffensen ◽  
Jonas Bergquist ◽  
Ariane Zamoner ◽  
...  

2003 ◽  
Vol 278 (45) ◽  
pp. 44808-44815 ◽  
Author(s):  
Masami Sakamoto ◽  
Hiromi Hirata ◽  
Toshiyuki Ohtsuka ◽  
Yasumasa Bessho ◽  
Ryoichiro Kageyama

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Paul J. Lucassen ◽  
Anne-Marie van Dam ◽  
Prasanna Kandel ◽  
Pascal Bielefeld ◽  
Aniko Korosi ◽  
...  

Abstract Neuroinflammation and neurogenesis have both been the subject of intensive investigation over the past 20 years. The sheer complexity of their regulation and their ubiquity in various states of health and disease have sometimes obscured the progress that has been made in unraveling their mechanisms and regulation. A recent study by Kozareva et al. (Neuronal Signaling (2019) 3), provides evidence that the orphan nuclear receptor TLX is central to communication between microglia and neural precursor cells and could help us understand how inflammation, mediated by microglia, influences the development of new neurons in the adult hippocampus. Here, we put recent studies on TLX into the context of what is known about adult neurogenesis and microglial activation in the brain, along with the many hints that these processes must be inter-related.


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