scholarly journals GENOMIC INSTABILITY IN THE BRAIN: ETIOLOGY, PATHOGENESIS AND NEW BIOLOGICAL MARKERS OF PSYCHIATRIC DISORDERS

2012 ◽  
Vol 67 (9) ◽  
pp. 45-53 ◽  
Author(s):  
A. S. Tiganov ◽  
Yu. B. Yurov ◽  
S. G. Vorsanova ◽  
I.Y Yu. Yurov
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
Genomic Instability ◽  
Genome Analysis ◽  
Biological Marker ◽  
Molecular Medicine ◽  
Therapeutic Practice ◽  
The Brain

The latest advances in molecular medicine, medical genetics and neurobiology have provided for a new look at processes occurring in cells of the brain and have allowed to discover previously unknown phenomena associated with mental traits and to propose new biomedical direction which include genomics, psychiatry and neurobiology ― brain genomics. The application of modern molecular and cellular technologies of genome analysis in the brain in common psychiatric disorders (autism, schizophrenia and Alzheimer’s disease) has shown that genomic instability is a phathogenetic mechanism of central nervous system abnormalities and plays a role in the brain development. Genomic disbalance alters neural homeostasis leads to cell death and is an important biological marker of psychiatric disorders which determine genomic pathways. These alterations lead to synaptic disfunction and neurodegeneration. In the present review, the main advances of brain genomics and potential application in diagnostic, clinical and therapeutic practice. 

Neurochemical Systems in the Central Nervous System

2013 ◽  
pp. 12-26
Author(s):  
Ariel Y. Deutch ◽  
Robert H. Roth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
Neurotrophic Factors ◽  
Drugs Of Abuse ◽  
Large Majority ◽  
System P ◽  
Target Neuron ◽  
The Central Nervous System ◽  
The Brain

Chapter 2 describes the neurochemical organization of the brain. It summarizes the diverse types of molecules that neurons in the brain use as neurotransmitters and neurotrophic factors, and how these molecules are synthesized and metabolized. The chapter also presents the array of receptor proteins through which these molecules regulate target neuron functioning and the reuptake proteins that generally terminate the neurotransmitter signal. Today a large majority of all drugs used to treat psychiatric disorders, as well as most drugs of abuse, still have as their initial targets proteins involved directly in neurotransmitter function.

scholarly journals A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2340
Author(s):  
Hannah E. Henson ◽  
Michael R. Taylor
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Developmental Defects ◽  
Whole Exome ◽  
The Central Nervous System ◽  
And Function ◽  
Upregulated Genes ◽  
The Brain

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.

Brain Protection by Erythropoietin: A Manifold Task

Physiology ◽  
2008 ◽  
Vol 23 (5) ◽  
pp. 263-274 ◽  
Author(s):  
Tamer Rabie ◽  
Hugo H. Marti
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Dominant Role ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Brain Protection ◽  
Hematopoietic Growth Factors ◽  
The Central Nervous System ◽  
The Brain

Many hematopoietic growth factors are produced locally in the brain. Among these, erythropoietin (Epo), has a dominant role for neuroprotection, neurogenesis, and acting as a neurotrophic factor in the central nervous system. These functions make erythropoietin a good candidate for treating diseases associated with neuronal cell death.

scholarly journals Bacterial inhibition of CD8+ T-cells mediated cell death promotes neuroinvasion and within-host persistence

2021 ◽  
Author(s):  
Marc Lecuit ◽  
Claire Maudet ◽  
Marouane Kheloufi ◽  
Sylvain Levallois ◽  
Julien Gaillard ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Cell Death ◽  
Nervous System ◽  
Cd8 T Cells ◽  
Cell Mediated Immunity ◽  
Dependent Manner ◽  
Central Nervous System Infections ◽  
Humanized Mouse Model ◽  
The Brain

Abstract Central nervous system infections are amongst the most severe, yet the mechanisms by which pathogens access the brain remain poorly understood. The model microorganism Listeria monocytogenes (Lm) is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest central nervous system infections. While immunosuppression is a well-established host risk factor for neurolisteriosis, little is known regarding the bacterial factors underlying Lm neuroinvasion. We have developed a clinically-relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains inoculated in a humanized mouse model of infection, and we show that the bacterial protein InlB protects infected monocytes from CD8+ T-cells Fas-mediated cell death, in a c-Met/PI3-kinase/FLIP-dependent manner. This blockade of anti-Lm specific cellular immune response lengthens infected monocytes lifespan, favoring Lm transfer from infected monocytes to the brain. The intracellular niche created by InlB-mediated cell-autonomous immunosuppression also promotes Lm fecal shedding, accounting for its selection as a Lm core virulence gene. Here, we have uncovered an unanticipated specific mechanism by which a bacterial pathogen confers to the cells it infects an increased lifespan by rendering them resistant to cell-mediated immunity. This promotes Lm within-host persistence and dissemination to the central nervous system, and transmission.

scholarly journals Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

2020 ◽  
Vol 21 (22) ◽  
pp. 8765 ◽  
Author(s):  
Cadiele Oliana Reichert ◽  
Fábio Alessandro de Freitas ◽  
Juliana Sampaio-Silva ◽  
Leonardo Rokita-Rosa ◽  
Priscila de Lima Barros ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Intracellular Iron ◽  
The Central Nervous System ◽  
The 1960S ◽  
The Brain

Ferroptosis is a type of cell death that was described less than a decade ago. It is caused by the excess of free intracellular iron that leads to lipid (hydro) peroxidation. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. Since the 1960s, increased concentration of iron in the central nervous system has been associated with oxidative stress, oxidation of proteins and lipids, and cell death. Here, we review the main mechanisms involved in the process of ferroptosis such as lipid peroxidation, glutathione peroxidase 4 enzyme activity, and iron metabolism. Moreover, the association of ferroptosis with the pathophysiology of some neurodegenerative diseases, namely Alzheimer’s, Parkinson’s, and Huntington’s diseases, has also been addressed.

scholarly journals Ferroptosis Mechanisms Involved in Hippocampal-Related Diseases

2021 ◽  
Vol 22 (18) ◽  
pp. 9902
Author(s):  
Xintong Wang ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong ◽  
Yaoxing Chen
Keyword(s):  
Lipid Peroxidation ◽  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Glutathione Metabolism ◽  
Intracellular Iron ◽  
System Disease ◽  
And Function ◽  
The Brain

Ferroptosis is a newly recognized type of cell death that is different from traditional forms of cell death, such as apoptosis, autophagy, and necrosis. It is caused by the accumulation of intracellular iron, promoting lipid peroxidation and leading to cell death. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. An increased concentration of iron in the central nervous system has been associated with oxidative stress, lipid peroxidation of proteins, and cell death. The hippocampus is an important brain region for learning, memory, and emotional responses, and is also a sensitive part of the brain to the dysfunctional homeostasis of transition metals. Damage of hippocampal structure and function are intimately involved in the pathogenic mechanisms underlying neurodegenerative diseases. Currently, ferroptosis is playing an increasingly important role in treatment areas of central nervous system diseases. Thus, we provide an overview of ferroptosis regulatory mechanisms, such as lipid metabolism, glutathione metabolism, and iron metabolism in this review. We also highlight the role of ferroptosis in hippocampal-related diseases and investigate a theoretical basis for further research on the role of ferroptosis in nervous system disease treatment.

scholarly journals Bacterial inhibition of CD8+ T-cells mediated cell death promotes neuroinvasion and within-host persistence

2020 ◽  
Author(s):  
Claire Maudet ◽  
Marouane Kheloufi ◽  
Sylvain Levallois ◽  
Julien Gaillard ◽  
Lei Huang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Cell Death ◽  
Nervous System ◽  
Virulence Gene ◽  
Cell Mediated Immunity ◽  
Dependent Manner ◽  
Central Nervous System Infections ◽  
Humanized Mouse Model ◽  
The Brain

AbstractCentral nervous system infections are amongst the most severe1,2, yet the mechanisms by which pathogens access the brain remain poorly understood. The model microorganism Listeria monocytogenes (Lm) is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest central nervous system infections3,4. While immunosuppression is a well-established host risk factor for neurolisteriosis3,5, little is known regarding the bacterial factors underlying Lm neuroinvasion. We have developed a clinically-relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains6 inoculated in a humanized mouse model of infection7, and we show that the bacterial protein InlB protects infected monocytes from CD8+ T-cells Fas-mediated cell death, in a c-Met/PI3-kinase/FLIP-dependent manner. This blockade of anti-Lm specific cellular immune response lengthens infected monocytes lifespan, favoring Lm transfer from infected monocytes to the brain. The intracellular niche created by InlB-mediated cell-autonomous immunosuppression also promotes Lm fecal shedding, accounting for its selection as a Lm core virulence gene. Here, we have uncovered an unanticipated specific mechanism by which a bacterial pathogen confers to the cells it infects an increased lifespan by rendering them resistant to cell-mediated immunity. This promotes Lm within-host persistence and dissemination to the central nervous system, and transmission.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Complex Trauma and Prenatal Alcohol Exposure: Clinical Implications

2012 ◽  
Vol 13 (2) ◽  
pp. 32-42 ◽  
Author(s):  
Yvette D. Hyter
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Child Development ◽  
Academic Outcomes ◽  
Complex Trauma ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Clinical Implications ◽  
Prenatal Alcohol ◽  
The Brain

Abstract Complex trauma resulting from chronic maltreatment and prenatal alcohol exposure can significantly affect child development and academic outcomes. Children with histories of maltreatment and those with prenatal alcohol exposure exhibit remarkably similar central nervous system impairments. In this article, I will review the effects of each on the brain and discuss clinical implications for these populations of children.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

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