scholarly journals Caspases in the Developing Central Nervous System: Apoptosis and Beyond

2021 ◽  
Vol 9 ◽  
Author(s):  
Trang Thi Minh Nguyen ◽  
Germain Gillet ◽  
Nikolay Popgeorgiev
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Synapse Formation ◽  
Current Knowledge ◽  
Cysteine Proteases ◽  
Mitochondrial Pathway ◽  
Neural Cells ◽  
Type I ◽  
Caspase Family

The caspase family of cysteine proteases represents the executioners of programmed cell death (PCD) type I or apoptosis. For years, caspases have been known for their critical roles in shaping embryonic structures, including the development of the central nervous system (CNS). Interestingly, recent findings have suggested that aside from their roles in eliminating unnecessary neural cells, caspases are also implicated in other neurodevelopmental processes such as axon guidance, synapse formation, axon pruning, and synaptic functions. These results raise the question as to how neurons regulate this decision-making, leading either to cell death or to proper development and differentiation. This review highlights current knowledge on apoptotic and non-apoptotic functions of caspases in the developing CNS. We also discuss the molecular factors involved in the regulation of caspase-mediated roles, emphasizing the mitochondrial pathway of cell death.

scholarly journals Differential Effects of Three CanonicalToxoplasmaStrains on Gene Expression in Human Neuroepithelial Cells

2010 ◽  
Vol 79 (3) ◽  
pp. 1363-1373 ◽  
Author(s):  
Jianchun Xiao ◽  
Lorraine Jones-Brando ◽  
C. Conover Talbot ◽  
Robert H. Yolken
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Nucleotide Metabolism ◽  
Neural Cells ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Neuroepithelial Cells ◽  
The Central Nervous System

ABSTRACTStrain type is one of the key factors suspected to play a role in determining the outcome ofToxoplasmainfection. In this study, we examined the transcriptional profile of human neuroepithelioma cells in response to representative strains ofToxoplasmaby using microarray analysis to characterize the strain-specific host cell response. The study of neural cells is of interest in light of the ability ofToxoplasmato infect the brain and to establish persistent infection within the central nervous system. We found that the extents of the expression changes varied considerably among the three strains. Neuroepithelial cells infected withToxoplasmatype I exhibited the highest level of differential gene expression, whereas type II-infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to the central nervous system, while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter the expression of a clearly defined set of genes. Moreover, Ingenuity Pathways Analysis (IPA) suggests that the three lineages differ in the ability to manipulate their host; e.g., they employ different strategies to avoid, deflect, or subvert host defense mechanisms. These observed differences may explain some of the variation in the neurobiological effects of different strains ofToxoplasmaon infected individuals.

MicroRNA-138-5p targets pro-apoptotic factors and favours neural cell survival

2020 ◽  
Author(s):  
Rodrigo M Maza ◽  
Agata Silvan ◽  
Teresa Muñoz-Galdeano ◽  
David Reigada ◽  
Ángela del Águila ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Cell Line ◽  
Neural Cell ◽  
Luciferase Reporter ◽  
Neural Cells ◽  
Qrt Pcr ◽  
The Central Nervous System ◽  
Apoptotic Genes

Abstract Background The central nervous system-enriched microRNA miR-138-5p becomes significantly downregulated after spinal cord injury (SCI). miR-138-5p modulates essential biological processes in the Central Nervous System (CNS). It also overcomes apoptosis by inhibiting the expression of proteins, including the effector CASP3, key in different cell death pathways. Therefore, we hypothesize that miR-138-5p downregulation following SCI underlies the overexpression of apoptotic genes and sensitizes neural cells to noxious stimuli. To confirm this hypothesis, this study aims a) to identify and validate miR-138-5p targets among the pro-apoptotic genes overexpressed following SCI; and b) to confirm that the miR-138-5p is able to modulate cell death in neural cells Methods We employed computational tools to identify potential pro-apoptotic targets of miR-138-5p. Dysregulation of selected targets after SCI and its relationship to changes in miR-138-5p expression were analysed through qRT-PCR in a rat SCI model. Validation of the regulation of those apoptotic targets was carried out by luciferase reporter, qRT-PCR, and immunoblot assays in cultures of neural cell lines transfected with a mimetic of the microRNA. The functional effects of modifying the expression of miR-138-5p were later examined in cultures of the rat neural cell line C6 employing enzymatic assays to measure the activity of effector CASP3 and CASP7 together with MTT and flow cytometry assays to estimate cell death. Results Consensus among different algorithms identified 209 potential targets of miR-138-5p. A total of 176 of them become dysregulated after SCI, including proteins basic to apoptosis process such as CASP3 and CASP7, or BAK (Bcl-2 homologous antagonist/killer). Downregulation of miR-138-5p after SCI correlates with the overexpression of these three targets. Cell culture analyses confirm that miR-138-5p targets their 3’UTRs and reduces their expression after microRNA transfection. Transfection of miR-138-5p in C6 cell line results in a reduced effector caspase activity and protects cells from apoptotic stimulation. Conclusions Our results demonstrate that downregulation of miR-138-5p after SCI can be deleterious to spinal neural cells. A mixture of direct effects mediated by the upregulation of apoptotic targets and indirect effects related to the upregulation of cell cycle proteins can be expected.

scholarly journals Plant Species of Sub-Family Valerianaceae—A Review on Its Effect on the Central Nervous System

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 846
Author(s):  
Gitishree Das ◽  
Han-Seung Shin ◽  
Rosa Tundis ◽  
Sandra Gonçalves ◽  
Ourlad Alzeus G. Tantengco ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Plant Species ◽  
Current Knowledge ◽  
Biological Properties ◽  
In Vivo Studies ◽  
Food Species ◽  
The Central Nervous System ◽  
Preclinical And Clinical Studies

Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispasmodic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valerianaofficinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed, Scopus, Sci Finder, Web of Science, Science Direct, NCBI, and Google Scholar. The search terms used for this review included Valerianaceae, Valeriana, Centranthus, Fedia, Patrinia, Nardostachys, Plectritis, and Valerianella, phytochemical composition, in vivo studies, Central Nervous System, neuroprotective, antidepressant, antinociceptive, anxiolytic, anxiety, preclinical and clinical studies.

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

2021 ◽  
Author(s):  
William E. Barclay ◽  
M. Elizabeth Deerhake ◽  
Makoto Inoue ◽  
Toshiaki Nonaka ◽  
Kengo Nozaki ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Animal Model ◽  
Cell Death ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammasome Activation ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.

Metallothionein prevents neurodegeneration and central nervous system cell death after treatment with gliotoxin 6-aminonicotinamide

2004 ◽  
Vol 77 (1) ◽  
pp. 35-53 ◽  
Author(s):  
Milena Penkowa ◽  
Albert Quintana ◽  
Javier Carrasco ◽  
Mercedes Giralt ◽  
Amalia Molinero ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Central Nervous System Cell ◽  
System Cell
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