scholarly journals The Thymus/Neocortex Hypothesis of the Brain: A Cell Basis for Recognition and Instruction of Self

2017 ◽  
Vol 11 ◽  
Author(s):  
Silvia Sánchez-Ramón ◽  
Florence Faure
Keyword(s):  
Cell Basis ◽  
A Cell ◽  
The Brain

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

scholarly journals Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takahiro Morito ◽  
Ryuichi Harada ◽  
Ren Iwata ◽  
Yiqing Du ◽  
Nobuyuki Okamura ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Post Injection ◽  
Affibody Molecule ◽  
Positron Emission ◽  
A Cell ◽  
Protein Binders ◽  
Rapid Clearance ◽  
Labelling Method ◽  
The Brain ◽  
Ex Vivo Study

AbstractBrain positron emission tomography (PET) imaging with radiolabelled proteins is an emerging concept that potentially enables visualization of unique molecular targets in the brain. However, the pharmacokinetics and protein radiolabelling methods remain challenging. Here, we report the performance of an engineered, blood–brain barrier (BBB)-permeable affibody molecule that exhibits rapid clearance from the brain, which was radiolabelled using a unique fluorine-18 labelling method, a cell-free protein radiosynthesis (CFPRS) system. AS69, a small (14 kDa) dimeric affibody molecule that binds to the monomeric and oligomeric states of α-synuclein, was newly designed for brain delivery with an apolipoprotein E (ApoE)-derived brain shuttle peptide as AS69-ApoE (22 kDa). The radiolabelled products 18F-AS69 and 18F-AS69-ApoE were successfully synthesised using the CFPRS system. Notably, 18F-AS69-ApoE showed higher BBB permeability than 18F-AS69 in an ex vivo study at 10 and 30 min post injection and was partially cleared from the brain at 120 min post injection. These results suggest that small, a brain shuttle peptide-fused fluorine-18 labelled protein binders can potentially be utilised for brain molecular imaging.

scholarly journals Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 229
Author(s):  
JunHyuk Woo ◽  
Hyesun Cho ◽  
YunHee Seol ◽  
Soon Ho Kim ◽  
Chanhyeok Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Computational Models ◽  
Neuronal Damage ◽  
Living Organism ◽  
The Body ◽  
Mitochondrial Functions ◽  
A Cell ◽  
The Brain ◽  
And Oxidative Stress

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

scholarly journals Anti-aggregation Effects of Phenolic Compounds on α-synuclein

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2444
Author(s):  
Kenjiro Ono ◽  
Mayumi Tsuji ◽  
Tritia R. Yamasaki ◽  
Giulio M. Pasinetti
Keyword(s):  
Phenolic Compounds ◽  
Gut Microbiota ◽  
Lewy Bodies ◽  
Hydroxybenzoic Acid ◽  
Dietary Polyphenols ◽  
Pathologic Features ◽  
Hydroxyphenylacetic Acid ◽  
A Cell ◽  
The Brain

The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson’s disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that attenuate αS aggregation and propagation. Based on cumulative evidence that αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies, we and other groups reported that phenolic compounds inhibit αS aggregation including oligomerization, thereby ameliorating αS oligomer-induced cellular and synaptic toxicities. Heterogeneity in gut microbiota may influence the efficacy of dietary polyphenol metabolism. Our recent studies on the brain-penetrating polyphenolic acids 3-hydroxybenzoic acid (3-HBA), 3,4-dihydroxybenzoic acid (3,4-diHBA), and 3-hydroxyphenylacetic acid (3-HPPA), which are derived from gut microbiota-based metabolism of dietary polyphenols, demonstrated an in vitro ability to inhibit αS oligomerization and mediate aggregated αS-induced neurotoxicity. Additionally, 3-HPPA, 3,4-diHBA, 3-HBA, and 4-hydroxybenzoic acid significantly attenuated intracellular αS seeding aggregation in a cell-based system. This review focuses on recent research developments regarding neuroprotective properties, especially anti-αS aggregation effects, of phenolic compounds and their metabolites by the gut microbiome, including our findings in the pathogenesis of α-synucleinopathies.

scholarly journals THE LEPTIN GENE IS A MARKER FOR THE CELL THERAPY OF METABOLIC SYNDROME

Biomeditsina ◽  
2019 ◽  
pp. 12-22
Author(s):  
N. V. Petrova
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Cell Therapy ◽  
Bone Marrow Cells ◽  
Liver And Pancreas ◽  
A Cell ◽  
Polymerase Chain ◽  
Lep Gene ◽  
The Brain

It is shown that the level of the Lep gene expression is a marker for B/Ks-Leprᵈᵇ/+ mice, which line serves as an optimal model for describing metabolic syndrome (MS) in preclinical studies. Mice were transplanted with cultured isogenic bone marrow cells (BMC) from heterozygous db/+ donors. The recipients were divided into two groups according to an early or advanced stage of MS development. We analyzed the expression of the Lep gene on the 3rd, 8th and 14th day following the administration of stem BMCs in the brain, liver and pancreas cells by polymerase chain reaction (PCR) in real time. The Lep gene expression was evaluated in terms of the number of cDNA copies. According to our data, leptin is a complete regulator of metabolic processes due to its effect on the hypothalamus, which, together with the hippocampus, controls the production of acetylcholine and insulin in the brain. We have proven the role of the Lep gene as a quantitative criterion for evaluating the effi cacy of a cell therapy in MS.

Light as a Life Tool

2020 ◽  
pp. 58-81
Author(s):  
John Parrington
Keyword(s):  
Fluorescent Protein ◽  
Green It ◽  
Live Animal ◽  
New Science ◽  
Gene Coding ◽  
A Cell ◽  
Electron Microscopes ◽  
First Time ◽  
Protein Channels ◽  
The Brain

Visual light, and radiation of other frequencies, are highly important for scientific research. The first light microscopes made it possible for the first time to see that organisms from plants to humans are composed of cells. Electron microscopes have allowed scientists to study the structural components of cells in great detail, and even determine the shapes of individual proteins. Many lifeforms also use light to attract a mate or prey, or deter an attacker. Following the identification of the gene coding for the fluorescent protein that makes certain jellyfish glow green it has become possible to use this to genetically label proteins in a living cell, or even a live animal. This means that now the location of proteins in a cell can be determined exactly. A major recent step forward in neuroscience came with the discovery of protein channels in algae that conduct ions in response to light. By creating transgenic mice that have these proteins in their brain neurons, it is now possible to modulate the activity of these neurons by shining light into the brain though microscopic fibre optic cables. This new science of optogenetics allows neurons to be switched on or off experimentally. The optogenetic approach has been used to uncover the neural circuits involved in memory, pain and pleasure. In the future this technique might be used to treat physical pain or depression in people. Controversially, it might be also be misused, to supress memories, or even create completely false ones in people’s heads.

Making (Bio)Logical Connections

2018 ◽  
Author(s):  
Subrata Dasgupta
Keyword(s):  
Cellular Automata ◽  
Universal Theory ◽  
Transition Rule ◽  
Yale University ◽  
Von Neumann ◽  
Finite Set ◽  
A Cell ◽  
The 1960S ◽  
The University ◽  
The Brain

At first blush, computing and biology seem an odd couple, yet they formed a liaison of sorts from the very first years of the electronic digital computer. Following a seminal paper published in 1943 by neurophysiologist Warren McCulloch and mathematical logician Warren Pitts on a mathematical model of neuronal activity, John von Neumann of the Institute of Advanced Study, Princeton, presented at a symposium in 1948 a paper that compared the behaviors of computer circuits and neuronal circuits in the brain. The resulting publication was the fountainhead of what came to be called cellular automata in the 1960s. Von Neumann’s insight was the parallel between the abstraction of biological neurons (nerve cells) as natural binary (on–off) switches and the abstraction of physical computer circuit elements (at the time, relays and vacuum tubes) as artificial binary switches. His ambition was to unify the two and construct a formal universal theory. One remarkable aspect of von Neumann’s program was inspired by the biology: His universal automata must be able to self-reproduce. So his neuron-like automata must be both computational and constructive. In 1955, invited by Yale University to deliver the Silliman Lectures for 1956, von Neumann chose as his topic the relationship between the computer and the brain. He died before being able to deliver the lectures, but the unfinished manuscript was published by Yale University Press under the title The Computer and the Brain (1958). Von Neumann’s definitive writings on self-reproducing cellular automata, edited by his one-time collaborator Arthur Burks of the University of Michigan, was eventually published in 1966 as the book Theory of Self-Reproducing Automata. A possible structure of a von Neumann–style cellular automaton is depicted in Figure 7.1. It comprises a (finite or infinite) configuration of cells in which a cell can be in one of a finite set of states. The state of a cell at any time t is determined by its own state and those of its immediate neighbors in the preceding point of time t – 1, according to a state transition rule.

Biodiversity as a source of new pharmacophores: A new theory of memory III

2005 ◽  
Vol 77 (1) ◽  
pp. 75-81 ◽  
Author(s):  
◽  
M. Iqbal Choudhary
Keyword(s):  
Natural Products ◽  
Anticancer Agents ◽  
Neurological Disorders ◽  
In Vitro Bioassay ◽  
Natural Sources ◽  
Chemical Basis ◽  
Antioxidant Agents ◽  
A Cell ◽  
The Brain

Several classes of natural products with significant inhibitory activity against target enzymes involved in several diseases have been identified. Spectrophotometer and high-throughput assays were used to assess the inhibition of prolyl endopeptidase (PEP), which led us to some novel inhibitors having potential as anticancer agents. Inhibition of cholinesterase enzymes has led to the discovery of new inhibitors with potential for use in Alzheimer’s disease and other neurological disorders. We have also discovered several potent antioxidant agents from natural sources by using a battery of antioxidant assays. Anti-inflammatory activity of a number of natural products was assayed through a cell-based in vitro bioassay. This article also contains a section on a slightly different topic of chemical basis of memory as presented during the lecture. The theory of the chemical basis of memory based on hydrogen bonding in the brain is further elaborated.

scholarly journals A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization

2011 ◽  
Vol 194 (2) ◽  
pp. 277-289 ◽  
Author(s):  
Zohreh Khavandgar ◽  
Christophe Poirier ◽  
Christopher J. Clarke ◽  
Jingjing Li ◽  
Nicholas Wang ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Skeletal Development ◽  
Specific Expression ◽  
Neutral Sphingomyelinase ◽  
Phosphodiesterase 3 ◽  
A Cell ◽  
Endocrine Factors ◽  
The Brain ◽  
Bone Abnormalities

A deletion mutation called fro (fragilitas ossium) in the murine Smpd3 (sphingomyelin phosphodiesterase 3) gene leads to a severe skeletal dysplasia. Smpd3 encodes a neutral sphingomyelinase (nSMase2), which cleaves sphingomyelin to generate bioactive lipid metabolites. We examined endochondral ossification in embryonic day 15.5 fro/fro mouse embryos and observed impaired apoptosis of hypertrophic chondrocytes and severely undermineralized cortical bones in the developing skeleton. In a recent study, it was suggested that nSMase2 activity in the brain regulates skeletal development through endocrine factors. However, we detected Smpd3 expression in both embryonic and postnatal skeletal tissues in wild-type mice. To investigate whether nSMase2 plays a cell-autonomous role in these tissues, we examined the in vitro mineralization properties of fro/fro osteoblast cultures. fro/fro cultures mineralized less than the control osteoblast cultures. We next generated fro/fro;Col1a1-Smpd3 mice, in which osteoblast-specific expression of Smpd3 corrected the bone abnormalities observed in fro/fro embryos without affecting the cartilage phenotype. Our data suggest tissue-specific roles for nSMase2 in skeletal tissues.

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