scholarly journals Remyelination-Promoting DNA Aptamer Conjugate Myaptavin-3064 Binds to Adult Oligodendrocytes In Vitro

2020 ◽  
Vol 13 (11) ◽  
pp. 403
Author(s):  
Mahboubeh Fereidan-Esfahani ◽  
Wei Ying Yue ◽  
Brandon Wilbanks ◽  
Aaron J. Johnson ◽  
Arthur E. Warrington ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immunoglobulin M ◽  
Dna Aptamer ◽  
Live Cells ◽  
Embryonic Mouse ◽  
Adult Rat ◽  
Cortical Cultures ◽  
Mixed Cortical Cultures

We previously applied Systematic Evolution of Ligands by EXponential enrichment (SELEX) technology to identify myelin-specific DNA aptamers, using crude mouse central nervous system myelin as bait. This selection identified a 40-nucleotide aptamer (LJM-3064). Multiple biotinylated LJM-3064 molecules were conjugated to a streptavidin core to mimic a multimeric immunoglobulin M (IgM) antibody, generating 3064-BS-streptavidin (Myaptavin-3064). We previously showed that Myaptavin-3064 induces remyelination in the Theiler’s murine encephalomyelitis virus (TMEV) model of chronic spinal cord demyelination. While details of target binding and the mechanism of action remain unclear, we hypothesized that Myaptavin-3064 induces remyelination by binding to oligodendrocytes (OLs). We now report the results of binding assays using the human oligodendroglioma (HOG) cell line, applying both flow cytometry and immunocytochemistry (IC) to assay aptamer conjugate binding to cells. IC assays were applied to compare aptamer conjugate binding to primary embryonic mouse mixed cortical cultures and primary adult rat mixed glial cultures. We show that Myaptavin-3064 binds to HOG cells, with increased binding upon differentiation. In contrast, a negative control aptamer conjugate, 3060-BS, which did not promote central nervous system (CNS) remyelination, does not bind to HOG cells. Myaptavin-3064 did not bind to lung (L2) or kidney (BHK) cell lines. Total internal reflection fluorescence (TIRF) imaging indicates that Myaptavin-3064 binds at the cell membrane of live cells. In addition to HOG cells, Myaptavin-3064 binds to adult rat OLs, but not to embryonic mouse mixed cortical cultures. These data support the hypothesis that Myaptavin-3064 binds to a surface molecule on both rodent and human OLs in a manner that triggers a remyelination signal pathway.

scholarly journals Tuberin levels during cellular differentiation in brain development

2021 ◽  
Author(s):  
Bashaer Abu Khatir ◽  
Gordon Omar Davis ◽  
Mariam Sameem ◽  
Rutu Patel ◽  
Jackie Fong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cell Lines ◽  
Neural Development ◽  
Time Course ◽  
Embryonic Mouse ◽  
Organ Systems ◽  
The Central Nervous System

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex, and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, lead to the formation of tumors and developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that Tuberin levels remain stable in the olfactory bulb but decrease in the Purkinje cell layer during embryonic mouse brain development. We show here that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. These data provide support for the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.

Oxidative and glycolytic pathways in rat (newborn and adult) and turtle brain: role during anoxia

1992 ◽  
Vol 262 (4) ◽  
pp. R595-R603 ◽  
Author(s):  
Y. Xia ◽  
C. Jiang ◽  
G. G. Haddad
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Stem ◽  
Brain Slices ◽  
Iodoacetic Acid ◽  
Adult Brain ◽  
Newborn Rats ◽  
Adult Rat

Using enzyme histochemistry and in vitro electrophysiological recordings in brain slices, we studied 1) the relative activity of cytochrome c oxidase (Cytox) and hexokinase (HK) and 2) cellular function by examining ionic homeostasis across cell membranes in the turtle and newborn (5 days old) and adult rat central nervous system. We found that Cytox was higher in the rostral than in the caudal brain regions of the adult rat and that the activity in the newborn is at least as high as in the adult rat. In contrast, adult turtles had very low Cytox activity throughout the central nervous system. Compared with that in the adult rat, HK activity in the newborn was generally lower in the rostral brain and cerebellum but similar or higher in the brain stem and spinal cord. In the turtle, HK activity was higher in the cerebellum, brain stem, and ventral horn of the spinal cord than in those in the rat. During anoxia, extracellular K+ increased by approximately 10-fold (from 3.2 to approximately 32 mM) in the adult brain stem but only by 2.6 mM in newborn rats. After glycolysis was blocked with iodoacetic acid (10-20 mM), extracellular K+ increased remarkably in both adult and newborn rats to approximately 35 mM. In contrast, the turtle brain tissue showed a slight and insignificant increase in extracellular K+ during complete anoxia or with iodoacetic acid; there was a modest increase in K+ when anoxia and iodoacetate were administered together. We conclude that 1) the newborn rat brain must rely either on higher glycolytic capacity or on a reduction of metabolic rate during O2 deprivation and 2) the turtle brain can subsist on nonglucose fuels or on fuels not requiring the citric acid cycle and the electron transfer chain.

scholarly journals Bombesin-Like, Substance P and Vasoactive Intestinal Polypeptide Receptors in Fetal Cortical Homografts to Host Cortex and Spinal Cord

1989 ◽  
Vol 1 (3-4) ◽  
pp. 105-112 ◽  
Author(s):  
Terry W. Moody ◽  
Reina L. Getz ◽  
William J. Goldberg ◽  
Jerald J. Bernstein
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Substance P ◽  
Vasoactive Intestinal Polypeptide ◽  
Peptide Receptors ◽  
Adult Rat ◽  
Graft Donor ◽  
Intestinal Polypeptide

Neuropeptide receptors were visualized in homografts of fetal cortex (E14) into adult rat cortex (immediate or 7 day delay) and spinal cord usingin vitroautoradiographic techniques to explore the expression of peptide receptors in the same graft tissue in different central nervous system implantation sites. Receptors for bombesin (BN)-like peptides developed in the grafts by 3 weeks postimplantation regardless of location or age of implantation pocket in host. After 4 weeks, the density of BN receptors was confined to the graft. In grafts to spinal cord, however, high densities of BN-like receptors were not confined to the graft but were distributed throughout the spinal cord. In contrast, the density of vasoactive intestinal polypeptide (VIP) and substance P (SP) receptors was moderate and low to undetectable in the fetal grafts. The development of the peptide receptors studied was graft donor tissue specific since they were not altered by central nervous system implantation site.

Neural Stem Cells to Glial Cells an Important Factor for Brain Injury

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Glial Cells ◽  
Brain Injuries ◽  
The Body ◽  
The Central Nervous System ◽  
Near Future

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.

scholarly journals Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2104 ◽  
Author(s):  
Eleonora Ficiarà ◽  
Shoeb Anwar Ansari ◽  
Monica Argenziano ◽  
Luigi Cangemi ◽  
Chiara Monge ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumors ◽  
Ad Hoc ◽  
Superparamagnetic Iron Oxide ◽  
Conventional Radiotherapy ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

scholarly journals Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

2021 ◽  
Vol 22 (4) ◽  
pp. 1725
Author(s):  
Diego Delgado ◽  
Ane Miren Bilbao ◽  
Maider Beitia ◽  
Ane Garate ◽  
Pello Sánchez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Response ◽  
Platelet Rich Plasma ◽  
Biological Response ◽  
In Vitro Models ◽  
Molecular Composition ◽  
Cellular Models ◽  
The Central Nervous System

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.

scholarly journals Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 848
Author(s):  
Luisa Stella Dolci ◽  
Rosaria Carmela Perone ◽  
Roberto Di Gesù ◽  
Mallesh Kurakula ◽  
Chiara Gualandi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Delivery System ◽  
Synergistic Effects ◽  
In Vitro Release ◽  
Health Priorities ◽  
The Central Nervous System ◽  
Vitro Release ◽  
Dual Drug

Vascular and traumatic injuries of the central nervous system are recognized as global health priorities. A polypharmacology approach that is able to simultaneously target several injury factors by the combination of agents having synergistic effects appears to be promising. Herein, we designed a polymeric delivery system loaded with two drugs, ibuprofen (Ibu) and thyroid hormone triiodothyronine (T3) to in vitro release the suitable amount of the anti-inflammation and the remyelination drug. As a production method, electrospinning technology was used. First, Ibu-loaded micro (diameter circa 0.95–1.20 µm) and nano (diameter circa 0.70 µm) fibers were produced using poly(l-lactide) PLLA and PLGA with different lactide/glycolide ratios (50:50, 75:25, and 85:15) to select the most suitable polymer and fiber diameter. Based on the in vitro release results and in-house knowledge, PLLA nanofibers (mean diameter = 580 ± 120 nm) loaded with both Ibu and T3 were then successfully produced by a co-axial electrospinning technique. The in vitro release studies demonstrated that the final Ibu/T3 PLLA system extended the release of both drugs for 14 days, providing the target sustained release. Finally, studies in cell cultures (RAW macrophages and neural stem cell-derived oligodendrocyte precursor cells—OPCs) demonstrated the anti-inflammatory and promyelinating efficacy of the dual drug-loaded delivery platform.

scholarly journals Absence of the αvβ3 Integrin Dictates the Time-Course of Angiogenesis in the Hypoxic Central Nervous System: Accelerated Endothelial Proliferation Correlates with Compensatory Increases in α5β1 Integrin Expression

2010 ◽  
Vol 30 (5) ◽  
pp. 1031-1043 ◽  
Author(s):  
Longxuan Li ◽  
Jennifer V Welser ◽  
Richard Milner
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Time Course ◽  
Αvβ3 Integrin ◽  
Integrin Expression ◽  
Brain Endothelial Cells ◽  
Endothelial Proliferation ◽  
Β3 Integrin ◽  
Α5β1 Integrin

Cerebral angiogenesis is an important adaptive response to hypoxia. As the αvβ3 integrin is induced on angiogenic vessels in the ischemic central nervous system (CNS), and the suggested angiogenic role for this integrin in other systems, it is important to determine whether the αvβ3 integrin is an important mediator of cerebral angiogenesis. αvβ3 integrin expression was examined in a model of cerebral hypoxia, in which mice were subject to hypoxia (8% O2) for 0, 4, 7, or 14 days. Immunofluorescence and western blot analysis revealed that in the hypoxic CNS, αvβ3 integrin was strongly induced on angiogenic brain endothelial cells (BEC), along with its ligand vitronectin. In the hypoxia model, β3 integrin-null mice showed no obvious defect in cerebral angiogenesis. However, early in the angiogenic process, BEC in these mice showed an increased mitotic index that correlated closely with increased α5 integrin expression. In vitro experiments confirmed α5 integrin upregulation on β3 integrin-null BEC, which also correlated with increased BEC proliferation on fibronectin. These studies confirm hypoxic induction of αvβ3 integrin on angiogenic vessels, but suggest distinct roles for the BEC integrins αvβ3 and α5β1 in cerebral angiogenesis, with αvβ3 having a nonessential role, and α5β1 promoting BEC proliferation.

scholarly journals INFLUENCE OF ANESTHESIA ON EXPERIMENTAL NEUROTROPIC VIRUS INFECTIONS

1946 ◽  
Vol 84 (4) ◽  
pp. 277-292 ◽  
Author(s):  
S. Edward Sulkin ◽  
Christine Zarafonetis ◽  
Andres Goth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Diethyl Ether ◽  
Cervical Region ◽  
Virus Infections ◽  
Ether Anesthesia ◽  
Neurotropic Virus ◽  
Experimental Infections

Anesthesia with diethyl ether significantly alters the course and outcome of experimental infections with the equine encephalomyelitis virus (Eastern or Western type) or with the St. Louis encephalitis virus. No comparable effect is observed in experimental infections produced with rabies or poliomyelitis (Lansing) viruses. The neurotropic virus infections altered by ether anesthesia are those caused by viruses which are destroyed in vitro by this anesthetic, and those infections not affected by ether anesthesia are caused by viruses which apparently are not destroyed by ether in vitro. Another striking difference between these two groups of viruses is their pathogenesis in the animal host; those which are inhibited in vivo by ether anesthesia tend to infect cells of the cortex, basal ganglia, and only occasionally the cervical region of the cord. On the other hand, those which are not inhibited in vivo by ether anesthesia tend to involve cells of the lower central nervous system and in the case of rabies, peripheral nerves. This difference is of considerable importance in view of the fact that anesthetics affect cells of the lower central nervous system only in very high concentrations. It is obvious from the complexity of the problem that no clear-cut statement can be made at this point as to the mechanism of the observed effect of ether anesthesia in reducing the mortality rate in certain of the experimental neurotropic virus infections. Important possibilities include a direct specific effect of diethyl ether upon the virus and a less direct effect of the anesthetic upon the virus through its alteration of the metabolism of the host cell.

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