scholarly journals Epileptogenesis due to glia-mediated synaptic scaling

2008 ◽  
Vol 6 (37) ◽  
pp. 655-668 ◽  
Author(s):  
Cristina Savin ◽  
Jochen Triesch ◽  
Michael Meyer-Hermann
Keyword(s):  
Immune System ◽  
Neuronal Activity ◽  
Activity Patterns ◽  
Brain Inflammation ◽  
Network Activity ◽  
Homeostatic Regulation ◽  
Synaptic Scaling ◽  
Tnf Α ◽  
Factor Α ◽  
Potential Interactions

Homeostatic regulation of neuronal activity is fundamental for the stable functioning of the cerebral cortex. One form of homeostatic synaptic scaling has been recently shown to be mediated by glial cells that interact with neurons through the diffusible messenger tumour necrosis factor-α (TNF-α). Interestingly, TNF-α is also used by the immune system as a pro-inflammatory messenger, suggesting potential interactions between immune system signalling and the homeostatic regulation of neuronal activity. We present the first computational model of neuron–glia interaction in TNF-α-mediated synaptic scaling. The model shows how under normal conditions the homeostatic mechanism is effective in balancing network activity. After chronic immune activation or TNF-α overexpression by glia, however, the network develops seizure-like activity patterns. This may explain why under certain conditions brain inflammation increases the risk of seizures. Additionally, the model shows that TNF-α diffusion may be responsible for epileptogenesis after localized brain lesions.

scholarly journals Atherosclerosis as Pathogenetic Substrate for Sars-Cov2 Cytokine Storm

2020 ◽  
Vol 9 (7) ◽  
pp. 2095 ◽  
Author(s):  
Mattia Vinciguerra ◽  
Silvia Romiti ◽  
Khalil Fattouch ◽  
Antonio De Bellis ◽  
Ernesto Greco
Keyword(s):  
Immune System ◽  
Viral Replication ◽  
Multiorgan Failure ◽  
Severe Infection ◽  
Adverse Outcomes ◽  
Alveolar Cells ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Plasmatic Concentration

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) outbreak is a public health emergency affecting different regions around the world. The lungs are often damaged due to the presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection varies from complete absence of symptomatology to more aggressive symptoms, characterized by sudden acute respiratory distress syndrome (ARDS), multiorgan failure, and sepsis, requiring treatment in intensive care unit (ICU). It is not still clear why the immune system is not able to efficiently suppress viral replication in a small percentage of patients. It has been documented as pathological conditions affecting the cardiovascular system, strongly associated to atherosclerotic progression, such as heart failure (HF), coronary heart disease (CHD), hypertension (HTN) and diabetes mellitus (DM), could serve as predictive factors for severity and susceptibility during Sars-CoV-2 infection. Atherosclerotic progression, as a chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory patterns, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1β. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results reported in severe COVID-19 infections, we hypothesized a pathogenetic correlation. Atherosclerosis may be an ideal pathogenetic substrate for high viral replication ability, leading to adverse outcomes, as reported in patients with cardiovascular factors. The level of atherosclerotic progression may affect a different degree of severe infection; in a vicious circle, feeding itself, Sars-CoV-2 may exacerbate atherosclerotic evolution due to excessive and aberrant plasmatic concentration of cytokines.

scholarly journals Imaging of respiratory-related population activity with single-cell resolution

2007 ◽  
Vol 292 (1) ◽  
pp. C508-C516 ◽  
Author(s):  
Frank Funke ◽  
Mathias Dutschmann ◽  
Michael Müller
Keyword(s):  
Single Cell ◽  
Neuronal Activity ◽  
Single Cells ◽  
Activity Patterns ◽  
Respiratory Rhythm ◽  
Network Activity ◽  
Respiratory Neurons ◽  
Ventrolateral Medulla ◽  
Population Activity ◽  
Respiratory Network

The pre-Bötzinger complex (PBC) in the rostral ventrolateral medulla contains a kernel involved in respiratory rhythm generation. So far, its respiratory activity has been analyzed predominantly by electrophysiological approaches. Recent advances in fluorescence imaging now allow for the visualization of neuronal population activity in rhythmogenic networks. In the respiratory network, voltage-sensitive dyes have been used mainly, so far, but their low sensitivity prevents an analysis of activity patterns of single neurons during rhythmogenesis. We now have succeeded in using more sensitive Ca2+ imaging to study respiratory neurons in rhythmically active brain stem slices of neonatal rats. For the visualization of neuronal activity, fluo-3 was suited best in terms of neuronal specificity, minimized background fluorescence, and response magnitude. The tissue penetration of fluo-3 was improved by hyperosmolar treatment (100 mM mannitol) during dye loading. Rhythmic population activity was imaged with single-cell resolution using a sensitive charge-coupled device camera and a ×20 objective, and it was correlated with extracellularly recorded mass activity of the contralateral PBC. Correlated optical neuronal activity was obvious online in 29% of slices. Rhythmic neurons located deeper became detectable during offline image processing. Based on their activity patterns, 74% of rhythmic neurons were classified as inspiratory and 26% as expiratory neurons. Our approach is well suited to visualize and correlate the activity of several single cells with respiratory network activity. We demonstrate that neuronal synchronization and possibly even network configurations can be analyzed in a noninvasive approach with single-cell resolution and at frame rates currently not reached by most scanning-based imaging techniques.

scholarly journals Tumor necrosis factor-α modulates GABAergic and Dopaminergic neurons in the ventral periaqueductal gray of female mice.

2021 ◽  
Author(s):  
Dipanwita Pati ◽  
Thomas L Kash
Keyword(s):  
Tumor Necrosis Factor ◽  
Neuronal Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Periaqueductal Gray ◽  
Synaptic Function ◽  
Gaba Neurons ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Neuroimmune signaling is increasingly identified as a critical component of various illnesses, including chronic pain, substance use disorder, and depression. However, the underlying neural mechanisms remain unclear. Proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), may play a key role by modulating synaptic function and long-term plasticity. The midbrain structure periaqueductal gray (PAG) plays a well-established role in pain processing, and while TNF-α inhibitors have emerged as a potential therapeutic strategy for pain-related disorders, the impact of TNF-α on PAG neuronal activity has not been thoroughly characterized. Recent studies have identified subpopulations of ventral PAG (vPAG) with opposing effects on nociception, with DA neurons driving pain relief in contrast to GABA neurons. Therefore, we used ex vivo slice physiology to examine the effects of TNF-α on neuronal activity of both subpopulations. We selectively targeted GABA and dopamine neurons using a vGAT-reporter and a TH-eGFP reporter mouse line, respectively. Following exposure to TNF-α, the intrinsic properties of GABA neurons were altered, resulting in increased excitability along with a reduction in glutamatergic synaptic drive. In DA neurons, TNF-α exposure resulted in a robust decrease in excitability along with a modest reduction in glutamatergic synaptic transmission. Furthermore, the effect of TNF-α was specific to excitatory transmission onto DA neurons as inhibitory transmission was unaltered. Collectively, these data suggest that TNF-α differentially affects the basal synaptic properties of GABA and DA neurons and enhances our understanding of how TNF-α mediated signaling modulates vPAG function.

149 PRODUCTION OF KNOCK-DOWN MICE WITH shRNA CYTOCHROME P-450 4F16 GENE AND REDUCTION OF THE IMMUNE SYSTEM

2012 ◽  
Vol 24 (1) ◽  
pp. 187
Author(s):  
B. C. Yang ◽  
K. C. Hwang ◽  
K. W. Kim ◽  
H. C. Lee ◽  
H. J. Chung ◽  
...  
Keyword(s):  
Immune System ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Wild Type ◽  
Knock Down ◽  
Tnf Α ◽  
C57bl Mice ◽  
Mrna And Protein Expression ◽  
Factor Α ◽  
Cytochrome P 450

The putative mouse homologue of cytochrome P-450 4F16 (Cyp4f16) is induced by interleukin-1 (Il-1), interleukin-6 (Il-6) and tumour necrosis factor-α (Tnf-α) and repressed by interleukin-10 (Il-10) and lipopolysaccharide (LPS). The Cyp4F16 is a subfamily of Cyp4F and it is also related to eicosanoids that are important mediators in the inflammatory cascade (Cui et al. 2001). To investigate the role of Cyp4F16, in the present study, we report the production of Cyp4f16 gene knock-down mice in 2 strains of mice, namely A/J and C57BL/6. The A/J is susceptible to infection and it is associated with Cyp4F16, whereas C57BL/6 is relatively resistant to infection. An shRNA-Cyp4F16 expression vector was microinjected into pronuclei of fertilized mouse oocytes and the embryos were transferred into pseudopregnant recipients. As a result, 25 and 50 mice were produced in the A/J and C57BL, respectively. Two mice in the A/J strain and 6 in the C57BL strain were confirmed by PCR as transgenic. Organs were collected in each of the lines produced by inbreeding and screened with real-time PCR for Cyp4f16 transcripts. The Cyp4f16 gene was expressed in a tissue-specific manner with high expression in the pancreas, spleen and lung and a lower level of transcription in the heart, muscle, thymus, kidney, testis and liver. In the spleen of transgenic Cyp4f16 knock-down mice, Cyp4f16 mRNA and protein expression levels were significantly lower than those of wild-type mice. The A/J Cyp4f16 knock-down mice suffered an inflammatory skin disease and tumours, but wild-type A/J mice and knock-down C57BL mice did not. Taken together, these results suggest that Cyp4f16 may play a regulatory role in the immune system and point to the use of the Cyp4f16 knock-down mouse as an experimental animal model for the study of the inflammatory process. This work was supported by a grant PJ0070762010 from BioGreen 21 Program, Rural Development Administration, Republic of Korea.

scholarly journals An in vivo Calcium Imaging Approach for the Identification of Cell-Type Specific Patterns in the Developing Cortex

2021 ◽  
Vol 15 ◽  
Author(s):  
Alicia Che ◽  
Natalia V. De Marco García
Keyword(s):  
Neuronal Activity ◽  
Neural Development ◽  
Activity Patterns ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Neuronal Diversity ◽  
Neuronal Populations ◽  
Cranial Window ◽  
Developing Neurons

Neuronal activity profoundly shapes the maturation of developing neurons. However, technical limitations have hampered the ability to capture the progression of activity patterns in genetically defined neuronal populations. This task is particularly daunting given the substantial diversity of pyramidal cells and interneurons in the neocortex. A hallmark in the development of this neuronal diversity is the participation in network activity that regulates circuit assembly. Here, we describe detailed methodology on imaging neuronal cohorts longitudinally throughout postnatal stages in the mouse somatosensory cortex. To capture neuronal activity, we expressed the genetically encoded calcium sensor GCaMP6s in three distinct interneuron populations, the 5HT3aR-expressing layer 1 (L1) interneurons, SST interneurons, and VIP interneurons. We performed cranial window surgeries as early as postnatal day (P) 5 and imaged the same cohort of neurons in un-anesthetized mice from P6 to P36. This Longitudinal two-photon imaging preparation allows the activity of single neurons to be tracked throughout development as well as plasticity induced by sensory experience and learning, opening up avenues of research to answer fundamental questions in neural development in vivo.

scholarly journals CAMU-CAMU (Myrciaria dubia (HBK) McVaugh), a small Amazonian fruit rich in vitamin C and a supplement for immunity

2021 ◽  
Vol 10 (6) ◽  
pp. e27810615877
Author(s):  
Ozanildo Vilaça do Nascimento ◽  
Emerson Lima Silva
Keyword(s):  
Immune System ◽  
Vitamin C ◽  
Inflammatory Diseases ◽  
Nutritional Composition ◽  
Infection Process ◽  
Cellular Damage ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Chemical Mediators

The Amazon Rainforest is rich in a diversity of species with various bioactive properties that have been widely used to treat a variety of inflammatory diseases. During the infection process, an oxidative stress environment is created that leads to cellular damage mediated by the transcription factor NF-kB, and triggers the production of pro-inflammatory chemical mediators, such as tumor necrosis factor-α [TNF-α] and interleukins IL-1β, IL-6, which causes a decline in the immune system. In this sense, the camu-camu fruit, which is native to the Amazon region, has in its nutritional composition several bioactive compounds and the highest level of vitamin C among Brazilian tropical fruits. It is also noted for its antioxidant and anti-inflammatory properties. Therefore, the objective of this review is to analyze the evidence collected in the literature regarding camu-camu as a functional food for the immune system in oxidative and inflammatory events.

scholarly journals MicroRNAs as the Important Regulators of T Helper 17 Cells: A Narrative Review

2020 ◽  
Author(s):  
Mahdi Atabaki ◽  
Zhaleh Shariati-Sarabi ◽  
Mehdi Barati ◽  
Jalil Tavakkol-Afshari ◽  
Mojgan Mohammadi
Keyword(s):  
Immune System ◽  
Cell Function ◽  
T Helper ◽  
T Helper 17 ◽  
Th17 Lymphocytes ◽  
Th 17 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

T helper (Th)-17 cells are a distinct and important subset of Th cells and their functions are due to the ability of production and secretion of key cytokines in the immune system such as interleukin (IL)-17, IL-22, IL-21, and tumor necrosis factor-α (TNF-α). According to these cytokines, these cells have vital roles in the pathogenesis of the disease such as rheumatoid arthritis (RA) and osteoarthritis (OA). Nowadays, microRNAs (miRNAs) are defined as essential regulators of cell function by targeting transcription factors and other elements that act in cells to control gene expression. The purpose of this study was to detect and investigate articles evaluating the function of miRNA in Th-17 cell performance. The language was restricted to English and the search was done in PubMed, Web of Science and Embase. In this review, we first explain the role of effective factors in the function of Th17 lymphocytes, and then, we summarize the performance of several miRNAs involved in the activation and appropriate functions of Th17 cells in the immune system.

Tumor necrosis factor-α modulates GABAergic and Dopaminergic neurons in the ventrolateral periaqueductal gray of female mice.

2021 ◽  
Author(s):  
Dipanwita Pati ◽  
Thomas L. Kash
Keyword(s):  
Tumor Necrosis Factor ◽  
Neuronal Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Female Mice ◽  
Glutamatergic Synaptic Transmission ◽  
Tnf Α ◽  
Factor Α ◽  
The Impact ◽  
Necrosis Factor

Neuroimmune signaling is increasingly identified as a critical component of various illnesses, including chronic pain, substance use disorder, and depression. However, the underlying neural mechanisms remain unclear. Proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), may play a role by modulating synaptic function and long-term plasticity. The midbrain structure periaqueductal gray (PAG) plays a well-established role in pain processing, and while TNF-α inhibitors have emerged as a therapeutic strategy for pain-related disorders, the impact of TNF-α on PAG neuronal activity has not been thoroughly characterized. Recent studies have identified subpopulations of ventrolateral PAG (vlPAG) with opposing effects on nociception, with dopamine (DA) neurons driving pain relief in contrast to GABA neurons. Therefore, we used slice physiology to examine the impact of TNF-α on neuronal activity of both these subpopulations. We focused on female mice since the PAG is a sexually dimorphic region and most studies use male subjects, limiting our understanding of mechanistic variations in females. We selectively targeted GABA and DA neurons using transgenic reporter lines. Following exposure to TNF-α there was an increase in excitability of GABA neurons along with a reduction in glutamatergic synaptic transmission. In DA neurons, TNF-α exposure resulted in a robust decrease in excitability along with a modest reduction in glutamatergic synaptic transmission. Interestingly, TNF-α had no effect on inhibitory transmission onto DA neurons. Collectively, these data suggest that TNF-α differentially affects the function of GABA and DA neurons in female mice and enhances our understanding of how TNF-α mediated signaling modulates vlPAG function.

scholarly journals UV Photoprotection, Cytotoxicity and Immunology Capacity of Red Algae Extracts

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 341 ◽  
Author(s):  
Félix Álvarez-Gómez ◽  
Nathalie Korbee ◽  
Virginia Casas-Arrojo ◽  
Roberto Abdala-Díaz ◽  
Félix Figueroa
Keyword(s):  
Immune System ◽  
Cell Lines ◽  
Human Keratinocytes ◽  
Human Cells ◽  
Array Detector ◽  
Ionization Mass ◽  
Protection Factor ◽  
Tnf Α ◽  
Factor Α

This study was designed to evaluate the potential use of algal extracts in cosmeceuticals, including factors related to biosecurity. The aqueous crude extracts of Hydropuntia cornea and Gracilariopsis longissima showed a good photoprotective capacity (Sun Protection Factor, SPF) due to, among other reasons, the presence of five types of mycosporine-like amino acids (MAAs) detected by high pressure liquid chromatography-photodiode array detector (HPLC-PDA) and electrospray ionization mass spectrometry (ESI-MS) (Palythine, Asterina-330, Shinorine, Porphyra-334, and Palythinol). The toxicity of the extracts was evaluated by the MTT assay, which is based on the metabolic reduction of MTT [3-(4,5-dimethylthiazol-2yl)-diphenyl tetrazolium bromide] by the action of the mitochondrial enzyme succinate dehydrogenase. This assay was carried out in vitro in three cell lines: one related to the immune system (murine macrophages of the immune system: RAW264.7) and two human cell lines related to the skin (gingival fibroblasts: HGF, and immortalized human keratinocytes: HaCaT). Both extracts showed no cytotoxic activity in both types of human cells, whereas they showed cytotoxicity in murine tumor cells of the immune system (macrophages: RAW264.7). On the other hand, the immunological activity in the murine macrophage RAW264.7 was studied at a concentration lower than 100 μg mL−1 and lower than the EC50, and evaluated by the production of pro-inflammatory compounds through an immunosorbent assay linked to enzymes such as tumor necrosis factor-α (TNF-α) or anti-inflammatory/proinflammatory enzymes such as interleukin-6 (IL-6). Both algae extracts induced the biosynthesis of TNF-α and IL-6. The production of TNF-α was much higher than that observed in the control (at a concentration of the aqueous extract higher than 5 μg mL−1). These results support the theory that the extracts of H. cornea and G. longissima actively induce the production of cytokines. In summary, the extracts of these species did not show cytotoxicity in human cells, and they present with immunomodulatory and photoprotection capacity.

Genetic Variation in TNF-α, its Relation with Inflammatory Biomarkers and Susceptibility to Rheumatoid Arthritis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Level ◽  
Functional Disability ◽  
Serum Levels ◽  
Amplification Refractory Mutation System ◽  
Reactive Protein ◽  
Tnf Α ◽  
Mutation System ◽  
Potential Factor ◽  
Factor Α

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.

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