scholarly journals CD60b: Enriching Neural Stem/Progenitor Cells from Rat Development into Adulthood

2017 ◽  
Vol 2017 ◽  
pp. 1-16
Author(s):  
Fernanda Gubert ◽  
Camila Zaverucha-do-Valle ◽  
Michelle Furtado ◽  
Pedro M. Pimentel-Coelho ◽  
Nicoli Mortari ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
System Development ◽  
Nervous System Development ◽  
Adult Brain ◽  
Neurogenic Niche ◽  
Neural Stem Progenitor Cells

CD60b antigens are highly expressed during development in the rat nervous system, while in the adult their expression is restricted to a few regions, including the subventricular zone (SVZ) around the lateral ventricles—a neurogenic niche in the adult brain. For this reason, we investigated whether the expression of C60b is associated with neural stem/progenitor cells in the SVZ, from development into adulthood. We performedin vitroandin vivoanalyses of CD60b expression at different stages and identified the presence of these antigens in neural stem/progenitor cells. We also observed that CD60b could be used to purify and enrich a population of neurosphere-forming cells from the developing and adult brain. We showed that CD60b antigens (mainly corresponding to ganglioside 9-O-acetyl GD3, a well-known molecule expressed during central nervous system development and mainly associated with neuronal migration) are also present in less mature cells and could be used to identify and isolate neural stem/progenitor cells during development and in the adult brain. A better understanding of molecules associated with neurogenesis may contribute not only to improve the knowledge about the physiology of the mammalian central nervous system, but also to find new treatments for regenerating tissue after disease or brain injury.

scholarly journals Drosophila Stathmin: A Microtubule-destabilizing Factor Involved in Nervous System Formation

2002 ◽  
Vol 13 (2) ◽  
pp. 698-710 ◽  
Author(s):  
Sylvie Ozon ◽  
Antoine Guichet ◽  
Olivier Gavet ◽  
Siegfried Roth ◽  
André Sobel
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Microtubule Assembly ◽  
Nervous Systems ◽  
Germ Cell Migration ◽  
Numerous Cell ◽  
First Time

Stathmin is a ubiquitous regulatory phosphoprotein, the generic element of a family of neural phosphoproteins in vertebrates that possess the capacity to bind tubulin and interfere with microtubule dynamics. Although stathmin and the other proteins of the family have been associated with numerous cell regulations, their biological roles remain elusive, as in particular inactivation of the stathmin gene in the mouse resulted in no clear deleterious phenotype. We identified stathmin phosphoproteins inDrosophila, encoded by a unique gene sharing the intron/exon structure of the vertebrate stathmin andstathmin family genes. They interfere with microtubule assembly in vitro, and in vivo when expressed in HeLa cells. Drosophila stathmin expression is regulated during embryogenesis: it is high in the migrating germ cells and in the central and peripheral nervous systems, a pattern resembling that of mammalian stathmin. Furthermore, RNA interference inactivation ofDrosophila stathmin expression resulted in germ cell migration arrest at stage 14. It also induced important anomalies in nervous system development, such as loss of commissures and longitudinal connectives in the ventral cord, or abnormal chordotonal neuron organization. In conclusion, a single Drosophilagene encodes phosphoproteins homologous to the entire vertebrate stathmin family. We demonstrate for the first time their direct involvement in major biological processes such as development of the reproductive and nervous systems.

Demyelination-remyelination in the Central Nervous System: Ligand-dependent Participation of the Notch Signaling Pathway

2019 ◽  
Vol 171 (1) ◽  
pp. 172-192 ◽  
Author(s):  
Patricia A Mathieu ◽  
María F Almeira Gubiani ◽  
Débora Rodríguez ◽  
Laura I Gómez Pinto ◽  
María de Luján Calcagno ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Central Nervous System Disease ◽  
Notch Signaling Pathway ◽  
Signaling Activation

Abstract Multiple sclerosis (MS) is an immune-mediated central nervous system disease mostly affecting young people. Multiple sclerosis and other neurodegenerative and white matter disorders involve oligodendrocyte (OL) damage and demyelination. Therefore, elucidating the signaling pathways involved in the remyelination process through the maturation of OL progenitor cells (OPCs) may contribute to the development of new therapeutic approaches. In this context, this paper further characterizes toxic cuprizone (CPZ)-induced demyelination and spontaneous remyelination in rats and investigates the role of ligand-dependent Notch signaling activation along demyelination/remyelination both in vivo and in vitro. Toxic treatment generated an inflammatory response characterized by both microgliosis and astrogliosis. Interestingly, early demyelination revealed an increase in the proportion of Jagged1+/GFAP+ cells, which correlated with an increase in Jagged1 transcript and concomitant Jagged1-driven Notch signaling activation, particularly in NG2+ OPCs, in both the corpus callosum (CC) and subventricular zone (SVZ). The onset of remyelination then exhibited an increase in the proportion of F3/contactin+/NG2+ cells, which correlated with an increase in F3/contactin transcript during ongoing remyelination in the CC. Moreover, neurosphere cultures revealed that neural progenitor cells present in the brain SVZ of CPZ-treated rats recapitulate in vitro the mechanisms underlying the response to toxic injury observed in vivo, compensating for mature OL loss. Altogether, the present results offer strong evidence of cell-type and ligand-specific Notch signaling activation and its time- and area-dependent participation in toxic demyelination and spontaneous remyelination.

Fibroblast growth factors as regulators of central nervous system development and function

2003 ◽  
Vol 284 (4) ◽  
pp. R867-R881 ◽  
Author(s):  
Rosanna Dono
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factors ◽  
System Development ◽  
Fibroblast Growth Factors ◽  
Brain Structures ◽  
Nervous System Development ◽  
Adult Brain ◽  
Fibroblast Growth ◽  
Fgf Signaling

Fibroblast growth factors (FGFs) are multifunctional signaling proteins that regulate developmental processes and adult physiology. Over the last few years, important progress has been made in understanding the function of FGFs in the embryonic and adult central nervous system. In this review, I will first discuss studies showing that FGF signaling is already required during formation of the neural plate. Next, I will describe how FGF signaling centers control growth and patterning of specific brain structures. Finally, I will focus on the function of FGF signaling in the adult brain and in regulating maintenance and repair of damaged neural tissues.

scholarly journals TDP-43 in central nervous system development and function: clues to TDP-43-associated neurodegeneration

2012 ◽  
Vol 393 (7) ◽  
pp. 589-594 ◽  
Author(s):  
Chantelle F. Sephton ◽  
Basar Cenik ◽  
Bercin Kutluk Cenik ◽  
Joachim Herz ◽  
Gang Yu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Interactions ◽  
System Development ◽  
Nervous System Development ◽  
Rna Targets ◽  
The Central Nervous System ◽  
And Function ◽  
Lateral Sclerosis

Abstract From the earliest stages of embryogenesis and throughout life, transcriptional regulation is carefully orchestrated in order to generate, shape, and reshape the central nervous system (CNS). TAR DNA-binding protein 43 (TDP-43) is identified as a regulator of essential transcriptional events in the CNS. Evidence for its importance comes from the identification of TDP-43 protein aggregates and genetic mutations in patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Efforts are being made to learn more about the biological function of TDP-43 and gain a better understanding of its role in neurodegeneration. TDP-43 RNA targets and protein interactions have now been identified, and in vivo evidence shows that TDP-43 is essential in CNS development and function. This review will highlight aspects of these findings.

scholarly journals The Monocarboxylate Transporter 8 Linked to Human Psychomotor Retardation Is Highly Expressed in Thyroid Hormone-Sensitive Neuron Populations

Endocrinology ◽  
2005 ◽  
Vol 146 (4) ◽  
pp. 1701-1706 ◽  
Author(s):  
Heike Heuer ◽  
Michael K. Maier ◽  
Sandra Iden ◽  
Jens Mittag ◽  
Edith C. H. Friesema ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Thyroid Hormone ◽  
System Development ◽  
Perinatal Period ◽  
Psychomotor Retardation ◽  
Nervous System Development ◽  
Monocarboxylate Transporter ◽  
Target Cells

Abstract Recent genetic analysis in several patients presenting a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels have revealed mutations or deletions in the gene of the monocarboxylate transporter 8 (MCT8). Because in vitro MCT8 functions as a TH transporter, the complex clinical picture of these patients indicated an important role for MCT8 in TH-dependent processes of brain development. To provide a clue to the cellular function of MCT8 in brain, we studied the expression of MCT8 mRNA in the murine central nervous system by in situ hybridization histochemistry. In addition to the choroid plexus structures, the highest transcript levels were found in neo- and allocortical regions (e.g. olfactory bulb, cerebral cortex, hippocampus, and amygdala), moderate signal intensities in striatum and cerebellum, and low levels in a few neuroendocrine nuclei. Colocalization studies revealed that MCT8 is predominantly expressed in neurons. Together with the spatiotemporal expression pattern of MCT8 during the perinatal period, these results strongly indicate that MCT8 plays an important role for proper central nervous system development by transporting TH into neurons as its main target cells.

scholarly journals Identification and Characterization of microRNAs during Retinoic Acid-Induced Regeneration of a Molluscan Central Nervous System

2018 ◽  
Vol 19 (9) ◽  
pp. 2741 ◽  
Author(s):  
Sarah Walker ◽  
Gaynor Spencer ◽  
Aleksandar Necakov ◽  
Robert Carlone
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retinoic Acid ◽  
Lymnaea Stagnalis ◽  
System Development ◽  
Growth Cones ◽  
Nervous System Development ◽  
Biologically Active ◽  
Sequencing Analysis

Retinoic acid (RA) is the biologically active metabolite of vitamin A and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By miRNA sequencing analysis, we identify 482 miRNAs in the regenerating central nervous system (CNS) of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up- or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate, for the first time, that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (pedal A), whereas expression in the growth cones of another class of respiratory motorneurons (right parietal A) was absent in vitro. These findings support our hypothesis that miRNAs are important regulators of retinoic acid-induced neuronal outgrowth and regeneration in regeneration-competent species.

scholarly journals Safe and Effective Cynomolgus Monkey GLP—Tox Study with Repetitive Intrathecal Application of a TGFBR2 Targeting LNA-Gapmer Antisense Oligonucleotide as Treatment Candidate for Neurodegenerative Disorders

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 200
Author(s):  
Sebastian Peters ◽  
Eva Wirkert ◽  
Sabrina Kuespert ◽  
Rosmarie Heydn ◽  
Siw Johannesen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nonhuman Primate ◽  
Neurodegenerative Disorders ◽  
Antisense Oligonucleotide ◽  
Clinical Chemistry ◽  
Cynomolgus Monkeys ◽  
Neurogenic Niche

The capability of the adult central nervous system to self-repair/regenerate was demonstrated repeatedly throughout the last decades but remains in debate. Reduced neurogenic niche activity paralleled by a profound neuronal loss represents fundamental hallmarks in the disease course of neurodegenerative disorders. We and others have demonstrated the endogenous TGFβ system to represent a potential pathogenic participant in disease progression, of amyotrophic lateral sclerosis (ALS) in particular, by generating and promoting a disequilibrium of neurodegenerative and neuroregenerative processes. The novel human/primate specific LNA Gapmer Antisense Oligonucleotide “NVP-13”, targeting TGFBR2, effectively reduced its expression and lowered TGFβ signal transduction in vitro and in vivo, paralleled by boosting neurogenic niche activity in human neuronal progenitor cells and nonhuman primate central nervous system. Here, we investigated NVP-13 in vivo pharmacology, safety, and tolerability following repeated intrathecal injections in nonhuman primate cynomolgus monkeys for 13 weeks in a GLP-toxicology study approach. NVP-13 was administered intrathecally with 1, 2, or 4 mg NVP-13/animal within 3 months on days 1, 15, 29, 43, 57, 71, and 85 in the initial 13 weeks. We were able to demonstrate an excellent local and systemic tolerability, and no adverse events in physiological, hematological, clinical chemistry, and microscopic findings in female and male Cynomolgus Monkeys. Under the conditions of this study, the no observed adverse effect level (NOAEL) is at least 4 mg/animal NVP-13.

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