scholarly journals Systemic Inflammation Accelerates Changes in Microglial and Synaptic Markers in an Experimental Model of Chronic Neurodegeneration

2022 ◽  
Vol 15 ◽  
Author(s):  
Joe K. Chouhan ◽  
Ursula Püntener ◽  
Steven G. Booth ◽  
Jessica L. Teeling
Keyword(s):  
Synaptic Plasticity ◽  
Bacterial Infection ◽  
Neurodegenerative Disease ◽  
Disease Progression ◽  
Systemic Inflammation ◽  
Immune Activation ◽  
Systemic Infection ◽  
Innate Immune ◽  
Low Grade ◽  
Synaptic Markers

Bacterial infections are a common cause of morbidity and mortality in the elderly, and particularly in individuals with a neurodegenerative disease. Experimental models of neurodegeneration have shown that LPS-induced systemic inflammation increases neuronal damage, a process thought to be mediated by activation of “primed” microglia. The effects of a real systemic bacterial infection on the innate immune cells in the brain and neuronal networks are less well described, and therefore, in this study we use the ME7 prion model to investigate the alterations in microglia activation and phenotype and synaptic markers in response to a low grade, live bacterial infection. Mice with or without a pre-existing ME7 prion-induced neurodegenerative disease were given a single systemic injection of live Salmonella typhimurium at early or mid-stage of disease progression. Immune activation markers CD11b and MHCII and pro-inflammatory cytokines were analyzed 4 weeks post-infection. Systemic infection with S. typhimurium resulted in an exaggerated inflammatory response when compared to ME7 prion mice treated with saline. These changes to inflammatory markers were most pronounced at mid-stage disease. Analysis of synaptic markers in ME7 prion mice revealed a significant reduction of genes that are associated with early response in synaptic plasticity, extracellular matrix structure and post-synaptic density, but no further reduction following systemic infection. In contrast, analysis of activity-related neuronal receptors involved in development of learning and memory, such as Grm1 and Grin2a, showed a significant decrease in response to systemic bacterial challenge. These changes were observed early in the disease progression and associated with reduced burrowing activity. The exaggerated innate immune activation and altered expression of genes linked to synaptic plasticity may contribute to the onset and/or progression of neurodegeneration.

Innate immune activation in neurodegenerative disease

2014 ◽  
Vol 14 (7) ◽  
pp. 463-477 ◽  
Author(s):  
Michael T. Heneka ◽  
Markus P. Kummer ◽  
Eicke Latz
Keyword(s):  
Neurodegenerative Disease ◽  
Immune Activation ◽  
Innate Immune ◽  
Innate Immune Activation

scholarly journals Investigating the mechanisms of brain innate immune activation following bacterial infection in Drosophila

2021 ◽  
Vol 17 (S12) ◽  
Author(s):  
Sameekshya Mainali ◽  
Luren Harper ◽  
Jordan Bolling ◽  
Kaitlin Berry ◽  
Elizabeth Kitchens ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Immune Activation ◽  
Innate Immune ◽  
Innate Immune Activation

scholarly journals NLRP3 and Infections: β-Amyloid in Inflammasome beyond Neurodegeneration

2021 ◽  
Vol 22 (13) ◽  
pp. 6984
Author(s):  
Giulia Sita ◽  
Agnese Graziosi ◽  
Patrizia Hrelia ◽  
Fabiana Morroni
Keyword(s):  
Systemic Inflammation ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Pathological Feature ◽  
Research Focus ◽  
Β Amyloid

Amyloid beta (Aβ)-induced abnormal neuroinflammation is recognized as a major pathological feature of Alzheimer’s disease (AD), which results in memory impairment. Research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease, or it is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, are crucial components of the innate immune system and are usually activated in response to infection or tissue damage. Although inflammasome activation plays critical roles against various pathogens in host defense, overactivation of inflammasome contributes to the pathogenesis of inflammatory diseases, including acute central nervous system (CNS) injuries and chronic neurodegenerative diseases, such as AD. This review summarizes the current literature on the role of the NLRP3 inflammasome in the pathogenesis of AD, and its involvement in infections, particularly SARS-CoV-2. NLRP3 might represent the crossroad between the hypothesized neurodegeneration and the primary COVID-19 infection.

scholarly journals Interplay between Peripheral and Central Inflammation in Obesity-Promoted Disorders: The Impact on Synaptic Mitochondrial Functions

2020 ◽  
Vol 21 (17) ◽  
pp. 5964 ◽  
Author(s):  
Marianna Crispino ◽  
Giovanna Trinchese ◽  
Eduardo Penna ◽  
Fabiano Cimmino ◽  
Angela Catapano ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Systemic Inflammation ◽  
Brain Plasticity ◽  
Leptin Resistance ◽  
Whole Body ◽  
Low Grade ◽  
Ros Production ◽  
Mitochondrial Functions ◽  
Metabolic Dysfunctions ◽  
The Impact

The metabolic dysfunctions induced by high fat diet (HFD) consumption are not limited to organs involved in energy metabolism but cause also a chronic low-grade systemic inflammation that affects the whole body including the central nervous system. The brain has been considered for a long time to be protected from systemic inflammation by the blood–brain barrier, but more recent data indicated an association between obesity and neurodegeneration. Moreover, obesity-related consequences, such as insulin and leptin resistance, mitochondrial dysfunction and reactive oxygen species (ROS) production, may anticipate and accelerate the physiological aging processes characterized by systemic inflammation and higher susceptibility to neurological disorders. Here, we discussed the link between obesity-related metabolic dysfunctions and neuroinflammation, with particular attention to molecules regulating the interplay between energetic impairment and altered synaptic plasticity, for instance AMP-activated protein kinase (AMPK) and Brain-derived neurotrophic factor (BDNF). The effects of HFD-induced neuroinflammation on neuronal plasticity may be mediated by altered brain mitochondrial functions. Since mitochondria play a key role in synaptic areas, providing energy to support synaptic plasticity and controlling ROS production, the negative effects of HFD may be more pronounced in synapses. In conclusion, it will be emphasized how HFD-induced metabolic alterations, systemic inflammation, oxidative stress, neuroinflammation and impaired brain plasticity are tightly interconnected processes, implicated in the pathogenesis of neurological diseases.

scholarly journals Altered Gut Microbiome Load and Immune Activation in a Drosophila Model of Human Tauopathy

2021 ◽  
Vol 15 ◽  
Author(s):  
Jerrik Rydbom ◽  
Halea Kohl ◽  
Vanesa R. Hyde ◽  
Kelly M. Lohr
Keyword(s):  
Neurodegenerative Disease ◽  
Immune Activation ◽  
Gut Microbiome ◽  
Chronic Traumatic Encephalopathy ◽  
Bacterial Load ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Food Distribution ◽  
Innate Immune ◽  
Transgenic Flies

Tau is a microtubule-associated protein that stabilizes the neuronal cytoskeleton. In the family of neurodegenerative diseases known as tauopathies, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), and chronic traumatic encephalopathy (CTE), abnormal tau aggregation destabilizes microtubule structure, contributing to a cascade of cellular processes leading to neuronal cell death. The gut microbiome has increasingly become a target of neurodegenerative disease research since gut microbiome imbalances have been linked to protein aggregation and inflammation through a bidirectional axis linking the gut and brain. Accordingly, the present study examined tau-mediated changes to gut microbiome composition and immune activation in a Drosophila melanogaster model of human mutant tauopathy. Fecal deposit quantification and gastric emptying time courses suggested an abnormal food distribution and reduced gut motility in tau transgenic flies compared to controls. Tau transgenic flies also showed an increase in gut bacteria colony forming units (CFUs) from diluted fly homogenate, indicating an increased bacterial load. Finally, we showed that tau transgenic flies have a trend towards elevated systemic levels of antimicrobial peptides targeting gram-negative bacteria using qPCR, suggesting an enhanced innate immune response to bacterial insult. These data demonstrate qualifiable and quantifiable gut microbial and innate immune responses to tauopathy. Furthermore, these results provide a framework for future studies targeting the gut microbiome as a modifier of neurodegenerative disease.

scholarly journals Neurodegenerative Disease and the NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Jonathan A. Holbrook ◽  
Heledd H. Jarosz-Griffiths ◽  
Emily Caseley ◽  
Samuel Lara-Reyna ◽  
James A. Poulter ◽  
...  
Keyword(s):  
Neurodegenerative Disease ◽  
Systemic Inflammation ◽  
Nlrp3 Inflammasome ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Low Grade ◽  
Crucial Component ◽  
Future Therapy ◽  
Global Population

The prevalence of neurodegenerative disease has increased significantly in recent years, and with a rapidly aging global population, this trend is expected to continue. These diseases are characterised by a progressive neuronal loss in the brain or peripheral nervous system, and generally involve protein aggregation, as well as metabolic abnormalities and immune dysregulation. Although the vast majority of neurodegeneration is idiopathic, there are many known genetic and environmental triggers. In the past decade, research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease or is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, a crucial component of the innate immune system, is usually activated in response to infection or tissue damage. Dysregulation of the NLRP3 inflammasome has been implicated in the progression of several neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. This review aims to summarise current literature on the role of the NLRP3 inflammasome in the pathogenesis of neurodegenerative diseases, and recent work investigating NLRP3 inflammasome inhibition as a potential future therapy.

Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 37-41 ◽  
Author(s):  
William F. Regine ◽  
Roy A. Patchell ◽  
James M. Strottmann ◽  
Ali Meigooni ◽  
Michael Sanders ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Disease Progression ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Content Type ◽  
Group B ◽  
Fine Print

Object. This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT). Methods. Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (≥ 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9–60 months). Six patients remained alive for 3 to 60 months. Conclusions. The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.

STUDY OF HS-CRP AND TNF-A LEVELS IN COPD PATIENTS ACCOMPANIED WITH CORONARY ARTERY DISEASE

2014 ◽  
pp. 48-56
Author(s):  
Van Thi Tran ◽  
Van Bang Le ◽  
Thị Thu Huong Hoang
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Systemic Inflammation ◽  
Chronic Obstructive ◽  
Low Grade ◽  
Cross Sectional ◽  
Copd Patients ◽  
Coronary Artery Angiography ◽  
Hs Crp ◽  
Artery Disease

Aim: Some studies have linked the present of chronic obstructive oulmonary disease (COPD) to coronary artery disease (CAD). Low grade systemic inflammation occurs in patients with COPD as well as patients with CAD. This study was designed to find out the concentration differences of hs-CRP and TNF-a in patients having both chronic obstructive pulmonary and coronary artery diseases with those having either. Methods: A cross - sectional descriptive study was conducted in 200 patients undergoing a coronary artery angiography in the Heart Institute, Thong Nhat Hospital and 115 People Hospital. COPD was diagnosed using GOLD classification. Result: Our study had shown that the levels of hs-CRP and TNF-a were statistically increased in patients with COPD, CAD as well as in patients who had COPD with CAD (p<0,05). The levels of hs-CRP were higher in CAD than in COPD nad the levels of TNF-a were higher in COPD than in CAD. In patients with COPD and CAD, there were increased the levels of both hs-CRP and TNF-a in serum. Conclusion: Systemic inflammation presents in both COPD and CAD. Key words: hs-CRP, TNF-a, coronary artery disease (CAD).

Sign in / Sign up

Export Citation Format

Share Document