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 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.

scholarly journals Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

2016 ◽  
Vol 84 (5) ◽  
pp. 1615-1632 ◽  
Author(s):  
Anke Osterloh ◽  
Stefanie Papp ◽  
Kristin Moderzynski ◽  
Svenja Kuehl ◽  
Ulricke Richardt ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Rickettsia Typhi ◽  
Content Type ◽  
Inflammatory Phenotype ◽  
Obligate Intracellular Bacteria ◽  
Immunocompromised Mice ◽  
The Brain

Rickettsioses are emerging febrile diseases caused by obligate intracellular bacteria belonging to the familyRickettsiaceae. Rickettsia typhibelongs to the typhus group (TG) of this family and is the causative agent of endemic typhus, a disease that can be fatal. In the present study, we analyzed the course ofR. typhiinfection in C57BL/6 RAG1−/−mice. Although these mice lack adaptive immunity, they developed only mild and temporary symptoms of disease and survivedR. typhiinfection for a long period of time. To our surprise, 3 to 4 months after infection, C57BL/6 RAG1−/−mice suddenly developed lethal neurological disorders. Analysis of these mice at the time of death revealed high bacterial loads, predominantly in the brain. This was accompanied by a massive expansion of microglia and by neuronal cell death. Furthermore, high numbers of infiltrating CD11b+macrophages were detectable in the brain. In contrast to the microglia, these cells harboredR. typhiand showed an inflammatory phenotype, as indicated by inducible nitric oxide synthase (iNOS) expression, which was not observed in the periphery. Having shown thatR. typhipersists in immunocompromised mice, we finally asked whether the bacteria are also able to persist in resistant C57BL/6 and BALB/c wild-type mice. Indeed,R. typhicould be recultivated from lung, spleen, and brain tissues from both strains even up to 1 year after infection. This is the first report demonstrating persistence and reappearance ofR. typhi, mainly restricted to the central nervous system in immunocompromised mice.

Protective peptides derived from novel glial proteins

2000 ◽  
Vol 28 (4) ◽  
pp. 452-455 ◽  
Author(s):  
D. E. Brenneman ◽  
C. Y. Spong ◽  
I. Gozes
Keyword(s):  
Oxidative Stress ◽  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Short Peptides ◽  
Significant Efficacy ◽  
The Central Nervous System ◽  
Human Neurodegenerative Disease

In studying the mediators of VIP neurotrophism in the central nervous system, two glial proteins have been discovered. Both of these proteins contain short peptides that exhibit femtomolar potency in preventing neuronal cell death from a wide variety of neurotoxic substances. Extension of these peptides to models of oxidative stress or neurodegeneration in vivo have indicated significant efficacy in protection. These peptides, both as individual agents and in combination, have promise as possible protective agents in the treatment of human neurodegenerative disease and in pathologies involving oxidative stress.

scholarly journals Upregulation of lncRNA147410.3 in the Brain of Mice With Chronic Toxoplasma Infection Promoted Microglia Apoptosis by Regulating Hoxb3

2021 ◽  
Vol 15 ◽  
Author(s):  
Yongliang Wang ◽  
Ruxia Han ◽  
Zhejun Xu ◽  
Xiahui Sun ◽  
Chunxue Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Target Gene ◽  
Neuronal Cell ◽  
Scientific Basis ◽  
Cns Development ◽  
Toxoplasma Infection ◽  
Key Factor ◽  
The Central Nervous System ◽  
The Brain

Toxoplasma gondii is neurotropic and affects the function of nerve cells, while the mechanism is unclear. LncRNAs are abundantly enriched in the brain and participated in the delicate regulation of the central nervous system (CNS) development. However, whether these lncRNAs are involved in the regulation of microglia activation during the process of T. gondii infection is largely unknown. In this study, the upregulation of a novel lncRNA147410.3 (ENSMUST00000147410.3) was identified as a key factor to influence this process. The target gene of lncRNA147410.3 was predicted and identified as Hoxb3. The localization of lncRNA147410.3 in the brain and cells was proved in the nucleus of neuroglia through FISH assay. Furthermore, the function of lncRNA147410.3 on neuronal cell was confirmed that lncRNA147410.3 could affect proliferation, differentiation, and apoptosis of mouse microglia by positively regulating Hoxb3. Thus, our study explored the modulatory action of lncRNA147410.3 in T. gondii infected mouse brain, providing a scientific basis for using lncRNA147410.3 as a therapeutic target to treat neurological disorder induced by T. gondii.

scholarly journals Coordinated Regulation and Widespread Cellular Expression of Interferon-Stimulated Genes (ISG) ISG-49, ISG-54, and ISG-56 in the Central Nervous System after Infection with Distinct Viruses

2006 ◽  
Vol 81 (2) ◽  
pp. 860-871 ◽  
Author(s):  
Christie Wacher ◽  
Marcus Müller ◽  
Markus J. Hofer ◽  
Daniel R. Getts ◽  
Regina Zabaras ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Dominant Role ◽  
Lymphocytic Choriomeningitis ◽  
Wild Type ◽  
Cellular Expression ◽  
The Central Nervous System ◽  
The Brain ◽  
Lcmv Infection

ABSTRACT The interferon (IFN)-stimulated genes (ISGs) ISG-49, ISG-54, and ISG-56 are highly responsive to viral infection, yet the regulation and function of these genes in vivo are unknown. We examined the simultaneous regulation of these ISGs in the brains of mice during infection with either lymphocytic choriomeningitis virus (LCMV) or West Nile virus (WNV). Expression of the ISG-49 and ISG-56 genes increased significantly during LCMV infection, being widespread and localized predominantly to common as well as distinct neuronal populations. Expression of the ISG-54 gene also increased but to lower levels and with a more restricted distribution. Although expression of the ISG-49, ISG-54, and ISG-56 genes was increased in the brains of LCMV-infected STAT1 and STAT2 knockout (KO) mice, this was blunted, delayed, and restricted to the choroid plexus, meninges, and endothelium. ISG-56 protein was regulated in parallel with the corresponding RNA transcript in the brain during LCMV infection in wild-type and STAT KO mice. Similar changes in ISG-49, ISG-54, and ISG-56 RNA levels and ISG-56 protein levels were observed in the brains of wild-type mice following infection with WNV. Thus, the ISG-49, ISG-54, and ISG-56 genes are coordinately upregulated in the brain during LCMV and WNV infection; this upregulation, in the case of LCMV, was totally (neurons) or partially (non-neurons) dependent on the IFN-signaling molecules STAT1 and STAT2. These findings suggest a dominant role for the ISG-49, ISG-54, and ISG-56 genes in the host response to different viruses in the central nervous system, where, particularly in neurons, these genes may have nonredundant functions.

scholarly journals Neurorestorative Roles of Microgliosis and Astrogliosis in Neuroinflammation and Neurodegeneration

2021 ◽  
Vol 1 (1) ◽  
pp. 1-5
Author(s):  
Babatunde Oluwafemi Adetuyi ◽  
◽  
Pere-Ebi Yabrade Toloyai ◽  
Evelyn Tarela Ojugbeli ◽  
Oyetola Tolulope Oyebanjo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Microglial Cell ◽  
Neuronal Cell ◽  
Biomechanical Properties ◽  
Neuronal Regeneration ◽  
Persistent Inflammation ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
The Brain

The pathophysiological processes involved in neurodegenerative diseases have not been clearly defined. Nevertheless, a significant aspect of the proof focuses directly on the function of several mechanisms of inflammation. The immune system is represented in the central nervous system by the microglial cell capable of detecting harmful or foreign pathogens, and thus initiates self-activation and neuro-inflammatory processes via phagocytosis and cytokines release, to maintain the cellular microenvironment. Then, microglial cells can spawn an emphasis on persistent inflammation that sometimes precedes or promote the neurodegenerative processes. Hence, the neuro-inflammatory micro-environment turns toxic and damaging to the neuronal cell, leading to degeneration and release of several factors which trigger an inflammatory reaction of the microglia, activating the neurodegenerative cycle. The biomechanical properties of the brain, neuronal regeneration, and plasticity can be modified by reactive gliosis. Defining the inception and development of reactive microgliosis and astrogliosis is vital for better clinical treatments design.

scholarly journals Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases

2018 ◽  
Vol 19 (10) ◽  
pp. 3082 ◽  
Author(s):  
Hao Chi ◽  
Hui-Yun Chang ◽  
Tzu-Kang Sang
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Alpha Synuclein ◽  
Adult Brain ◽  
Pathological Feature ◽  
The Central Nervous System ◽  
Cell Death Mechanisms ◽  
The Brain

Neuronal cell death in the central nervous system has always been a challenging process to decipher. In normal physiological conditions, neuronal cell death is restricted in the adult brain, even in aged individuals. However, in the pathological conditions of various neurodegenerative diseases, cell death and shrinkage in a specific region of the brain represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe evidence for cell death in the context of individual common neurodegenerative diseases, discussing our current understanding of cell death by connecting with renowned pathogenic proteins, including Tau, amyloid-beta, alpha-synuclein, huntingtin and TDP-43.

scholarly journals Role of Grina/Nmdara1 in the Central Nervous System Diseases

2020 ◽  
Vol 18 (9) ◽  
pp. 861-867
Author(s):  
Kai Chen ◽  
Liu Nan Yang ◽  
Chuan Lai ◽  
Dan Liu ◽  
Ling-Qiang Zhu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Diseases ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Human Beings ◽  
Major Depressive ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Glutamate receptor, ionotropic, N-methyl-D-aspartate associated protein 1 (GRINA) is a member of the NMDA receptors (NMDARs) and is involved in several neurological diseases, which governs the key processes of neuronal cell death or the release of neurotransmitters. Upregulation of GRINA has been reported in multiple diseases in human beings, such as major depressive disorder (MDD) and schizophrenia (SCZ), with which the underlying mechanisms remain elusive. In this review, we provide a general overview of the expression and physiological function of GRINA in the central nervous system (CNS) diseases, including stroke, depression ,epilepsy, SCZ, and Alzheimer’s disease (AD).

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.

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