scholarly journals Aragonite-Polylysine: Neuro-Regenerative Scaffolds with Diverse Effects on Astrogliosis

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 2850
Author(s):  
Tzachy Morad ◽  
Roni Mina Hendler ◽  
Eyal Canji ◽  
Orly Eva Weiss ◽  
Guy Sion ◽  
...  

Biomaterials, especially when coated with adhesive polymers, are a key tool for restorative medicine, being biocompatible and supportive for cell adherence, growth, and function. Aragonite skeletons of corals are biomaterials that support survival and growth of a range of cell types, including neurons and glia. However, it is not known if this scaffold affects neural cell migration or elongation of neuronal and astrocytic processes, prerequisites for initiating repair of damage in the nervous system. To address this, hippocampal cells were aggregated into neurospheres and cultivated on aragonite skeleton of the coral Trachyphyllia geoffroyi (Coral Skeleton (CS)), on naturally occurring aragonite (Geological Aragonite (GA)), and on glass, all pre-coated with the oligomer poly-D-lysine (PDL). The two aragonite matrices promoted equally strong cell migration (4.8 and 4.3-fold above glass-PDL, respectively) and axonal sprouting (1.96 and 1.95-fold above glass-PDL, respectively). However, CS-PDL had a stronger effect than GA-PDL on the promotion of astrocytic processes elongation (1.7 vs. 1.2-fold above glass-PDL, respectively) and expression of the glial fibrillary acidic protein (3.8 vs. and 1.8-fold above glass-PDL, respectively). These differences are likely to emerge from a reaction of astrocytes to the degree of roughness of the surface of the scaffold, which is higher on CS than on GA. Hence, CS-PDL and GA-PDL are scaffolds of strong capacity to derive neural cell movements and growth required for regeneration, while controlling the extent of astrocytic involvement. As such, implants of PDL-aragonites have significant potential as tools for damage repair and the reduction of scar formation in the brain following trauma or disease.

The Neuron ◽  
2015 ◽  
pp. 23-38
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek

This chapter examines unique mechanisms that the neuron has evolved to establish and maintain the form required for its specialized signaling functions. Unlike some other organs, the brain contains a variety of cell types including several classes of glial cells, which play a critical role in the formation of the myelin sheath around axons and may be involved in immune responses, synaptic transmission, and long-distance calcium signaling in the brain. Neurons share many features in common with other cells (including glia), but they are distinguished by their highly asymmetrical shapes. The neuronal cytoskeleton is essential for establishing this cell shape during development and for maintaining it in adulthood. The process of axonal transport moves vesicles and other organelles to regions remote from the neuronal cell body. Proteins such as kinesin and dynein, called molecular motors, make use of the energy released by hydrolysis of ATP to drive axonal transport.


2015 ◽  
Vol 112 (22) ◽  
pp. 6800-6806 ◽  
Author(s):  
Benyam Kinde ◽  
Harrison W. Gabel ◽  
Caitlin S. Gilbert ◽  
Eric C. Griffith ◽  
Michael E. Greenberg

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.


1998 ◽  
Vol 18 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Ursula Sonnewald ◽  
Leif Hertz ◽  
Arne Schousboe

Classically, compartmentation of glutamate metabolism in the brain is associated with the fact that neurons and glia exhibit distinct differences with regard to metabolism of this amino acid. The recent use of 13C-labeled compounds to study this metabolism in conjunction with the availability of cell type-specific tissue culture modes has led to the notion that such compartmentation may even be present in individual cell types, neurons as well as glia. To better understand and explain this, it is proposed that mitochondrial heterogeneity may exist resulting in tricarboxylic acid cycles with different properties regarding cycling rates and ratio as well as coupling to amino acid biosynthesis, primarily involving glutamate and aspartate. These hypotheses are evaluated in the light of current knowledge about mitochondrial structure and function.


2019 ◽  
Author(s):  
Sooyeon Yoo ◽  
David Cha ◽  
Dong Won Kim ◽  
Thanh V. Hoang ◽  
Seth Blackshaw

AbstractLeptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for leptin receptor (LepR) expression is lacking, and the effect of tanycyte-specific deletion of LepR has not been investigated. In this study, we analyze the expression and function of the tanycytic LepR in mice. Using single-molecule fluorescent in situ hybridization (smfISH), RT-qPCR, single-cell RNA sequencing (scRNA-Seq), and selective deletion of the LepR in tanycytes, we are unable to detect expression of LepR in the tanycytes. Tanycyte-specific deletion of LepR likewise did not affect leptin-induced pSTAT3 expression in hypothalamic neurons, regardless of whether leptin was delivered by intraperitoneal or intracerebroventricular injection. Finally, we use activity-regulated scRNA-Seq (act-Seq) to comprehensively profile leptin-induced changes in gene expression in all cell types in mediobasal hypothalamus. Clear evidence for leptin signaling is only seen in endothelial cells and subsets of neurons, although virtually all cell types show leptin-induced changes in gene expression. We thus conclude that LepR expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling through a LepR-dependent mechanism, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms.


Author(s):  
V. F. Allison ◽  
R. S. Sohal

Relatively little is known regarding the structure and function of glial cells in the brain of invertebrate organisms. Fine structural aspects of the interrelationships between glial cells and neurons in the brain of the housefly are described. Three types of glial cells have been identified in the brain of the housefly. Cell bodies of the neurons and two glial cell types are located at the periphery of the brain and surround a centrally located neuropil. Soma of the neurons are completely surrounded by a single or multiple layers of glioplasm which precludes the existence of synaptic sites on the cell body (Fig. 1). Synaptic sites are restricted to the neuropil region. Thin processes of glioplasm also invaginated the perikaryon.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2507
Author(s):  
Carla Mucignat-Caretta

The brain may be affected by a variety of tumors of different grade, which originate from different cell types at distinct locations, thus impacting on the brain structure and function [...]


2021 ◽  
Vol 220 (7) ◽  
Author(s):  
Isha Ralhan ◽  
Chi-Lun Chang ◽  
Jennifer Lippincott-Schwartz ◽  
Maria S. Ioannou

Lipid droplets are dynamic intracellular lipid storage organelles that respond to the physiological state of cells. In addition to controlling cell metabolism, they play a protective role for many cellular stressors, including oxidative stress. Despite prior descriptions of lipid droplets appearing in the brain as early as a century ago, only recently has the role of lipid droplets in cells found in the brain begun to be understood. Lipid droplet functions have now been described for cells of the nervous system in the context of development, aging, and an increasing number of neuropathologies. Here, we review the basic mechanisms of lipid droplet formation, turnover, and function and discuss how these mechanisms enable lipid droplets to function in different cell types of the nervous system under healthy and pathological conditions.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Emily W Baker ◽  
Simon R Platt ◽  
Shannon P Holmes ◽  
Liya Wang ◽  
Vivian W Lau ◽  
...  

Studies in rodents have provided evidence that induced pluripotent stem cell derived neural stem cells (iNSCs) have a multifunctional role in stroke recovery. iNSCs mitigate tissue loss due to secondary injury, promote tissue recovery through angiogenesis, and differentiate into mature neural cell types resulting in recovery and replacement of lost and damaged brain tissue. However, many stroke therapies developed in the rodent have failed in clinical trials, suggesting that iNSC therapy should be tested in a more translatable large animal model such as the pig. The objective of this study was to assess the ability of iNSCs to differentiate into mature neural cell types and characterize the effects of iNSCs on brain tissue recovery utilizing non-invasive magnetic resonance imaging (MRI) and spectroscopy approaches in a pig model. Eight male landrace pigs underwent middle cerebral artery occlusion stroke surgery. After 5 days, 4 pigs received iNSC intraparenchymal injections and 4 pigs received vehicle only injections. Pigs underwent MRI assessment at 24 hrs post-stroke and 1, 4, and 12 wks post-injection, and brain tissues were collected 12 wks post-injection. At 12 wks post-injection, iNSC treated pigs showed significant improvement in white matter integrity with recovery of fractional anisotropy being 4-fold higher in treated pigs relative to non-treated pigs. Perfusion weighted imaging demonstrated significant improvement in cerebral blood volume (13%), time to peak (36%), and mean transit time (41%) in treated pigs at 12 wks post-injection vs. non-treated pigs. In addition, treated pigs showed significant improvement in neurometabolites NAA, Cr, and Cho at 12 wks post-injection relative to non-treated pigs. Gene expression analysis established significant increases in neurotrophic and angiogenic factors including BDNF and ANG1, respectively, in brain tissue of treated pigs vs. non-treated pigs suggesting potential modes of action. iNSCs were located in the brain parenchyma 12 wks post-injection, and the majority were positive for the mature neuronal marker NeuN. These results demonstrated that iNSCs are capable of neuronal differentiation and long term integration while promoting tissue recovery in a preclinical pig ischemic stroke model.


2005 ◽  
Vol 201 (10) ◽  
pp. 1579-1589 ◽  
Author(s):  
Mei Massengale ◽  
Amy J. Wagers ◽  
Hannes Vogel ◽  
Irving L. Weissman

Several studies have reported that bone marrow (BM) cells may give rise to neurons and astrocytes in vitro and in vivo. To further test this hypothesis, we analyzed for incorporation of neural cell types expressing donor markers in normal or injured brains of irradiated mice reconstituted with whole BM or single, purified c-kit+Thy1.1loLin−Sca-1+ (KTLS) hematopoietic stem cells (HSCs), and of unirradiated parabionts with surgically anastomosed vasculature. Each model showed low-level parenchymal engraftment of donor-marker+ cells with 96–100% immunoreactivity for panhematopoietic (CD45) or microglial (Iba1 or Mac1) lineage markers in all cases studied. Other than one arborizing structure in the olfactory bulb of one BM-transplanted animal, possibly representing a neuronal or glial cell process, we found no donor-marker–expressing astrocytes or non-Purkinje neurons among >10,000 donor-marker+ cells from 21 animals. These data strongly suggest that HSCs and their progeny maintain lineage fidelity in the brain and do not adopt neural cell fates with any measurable frequency.


Sign in / Sign up

Export Citation Format

Share Document