The semantics of microglia activation: neuroinflammation, homeostasis, and stress

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: Nov. 6, 2021

Microglia are emerging as critical regulators of neuronal function and behavior in nearly every area neuroscience. Initial reports focused on classical immune functions microglia pathological contexts, however, immunological concepts from these studies have been applied to describe neuro-immune interactions the absence disease, injury, or infection. Indeed, terms such 'microglia activation' 'neuroinflammation' used ubiquitously changes disparate contexts; particularly stress research, where prompt undue comparisons conditions. This creates a barrier for investigators new neuro-immunology ultimately hinders our understanding effects microglia. As more seek understand role neurobiology behavior, it is increasingly important develop standard methods study define microglial phenotype function. In this review, we summarize primary research physiological contexts. Further, propose framework better microglia1 chronic stress. approach will enable precise characterization different which should facilitate development microglia-directed therapeutics psychiatric neurological disease.

Language: Английский

---

Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Sept. 13, 2021

Neuroinflammation is involved in the onset or progression of various neurodegenerative diseases. Initiation neuroinflammation triggered by endogenous substances (damage-associated molecular patterns) and/or exogenous pathogens. Activation glial cells (microglia and astrocytes) widely recognized as a hallmark triggers release proinflammatory cytokines, leading to neurotoxicity neuronal dysfunction. Another feature associated with neuroinflammatory diseases impairment blood-brain barrier (BBB). The BBB, which composed brain endothelial connected tight junctions, maintains homeostasis protects neurons. Impairment this allows trafficking immune plasma proteins into parenchyma subsequent inflammatory processes brain. Besides neurons, activated also affect BBB integrity. Therefore, dysfunction can amplify act key process development neuroinflammation. integrity determined integration multiple signaling pathways within through intercellular communication between perivascular (pericytes, astrocytes, microglia, oligodendrocytes). For prevention disruption, both cellular components, such molecules cells, non-cellular mediators released should be considered. Thus, understanding intracellular that disrupt provide novel treatments for neurological In review, we discuss current knowledge regarding underlying mechanisms cells.

Language: Английский

---

Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 22(3), P. 185 - 212

Published: Dec. 21, 2022

Language: Английский

---

Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer’s disease (MCI and dementia) in primary care: a review and synthesis

Journal of Internal Medicine, Journal Year: 2021, Volume and Issue: 290(2), P. 310 - 334

Published: Jan. 18, 2021

Abstract The critical role of primary care clinicians (PCCs) in Alzheimer’s disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms disease‐modifying therapies (DMTs) emerge. Our understanding AD has grown substantially: no longer conceptualized a late‐in‐life syndrome cognitive functional impairments, we now recognize that pathology builds silently for decades before impairment is detectable. Clinically, first manifests subtly mild (MCI) due to progressing dementia. Emerging optimism improved outcomes stems from focus on preventive interventions midlife timely, biomarker‐confirmed at early signs deficits (i.e. MCI dementia). A timely particularly important optimizing patient enabling the appropriate use anticipated DMTs. An accelerating challenge PCCs specialists will be respond innovations diagnostics therapy system not currently well positioned do so. To overcome these challenges, collaborate closely navigate optimize dynamically evolving face opportunities. In spirit this collaboration, summarize here some prominent influential models inform our current AD. We also advocate accurate biomarker‐defined) doing so, consider issues related detecting emerging biomarkers clinic.

Language: Английский

---

Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 5023 - 5023

Published: April 30, 2022

Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical composition, and/or absorption. Depending on targeted processes within living organism, different are used for various medical conditions, such as cancer, particular brain pathologies, cardiac events, bone lesions, where most commonly radiolabeled with 18F (e.g., [

Language: Английский

---

Diagnostic biomarkers of Alzheimer’s disease: A state-of-the-art review

Biomarkers in Neuropsychiatry, Journal Year: 2019, Volume and Issue: 1, P. 100005 - 100005

Published: Nov. 13, 2019

In 2018, there was a recent shift towards biological definition of Alzheimer's disease (AD), based on biomarkers measured in vivo even before the onset clinical dementia symptoms. No single biomarker can by itself accurately diagnose AD. A combination assessed through imaging and cerebrospinal fluid (CSF) yields better diagnostic accuracy. Although amyloid PET CSF levels tau deposits are increasingly used AD trials to increase confidence enrolled subjects, routine use these settings is still premature because risk overdiagnosis, increased cost and/or invasiveness assessment method. Also, standardization measures across studies needed assure regulatory approval. Exploring novel beyond pathologies, their longitudinal change continnum important research avenues for future.

Language: Английский

---

The physiology of regulated BDNF release

Cell and Tissue Research, Journal Year: 2020, Volume and Issue: 382(1), P. 15 - 45

Published: Sept. 18, 2020

Abstract The neurotrophic factor BDNF is an important regulator for the development of brain circuits, synaptic and neuronal network plasticity, as well neuroregeneration neuroprotection. Up- downregulations levels in human blood tissue are associated with, e.g., neurodegenerative, neurological, or even cardiovascular diseases. changes concentration caused by altered dynamics expression release. To understand relevance major variations levels, detailed knowledge regarding physiological pathophysiological stimuli affecting intra- extracellular important. Most work addressing molecular cellular regulation release have been performed preparations. Therefore, this review will summarize inducing BDNF, mechanisms regulating efficacy release, with a focus on cells originating from brain. Further, we discuss current about distinct eliciting regulated under conditions.

Language: Английский

---

Cellular sources of TSPO expression in healthy and diseased brain

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2021, Volume and Issue: 49(1), P. 146 - 163

Published: Jan. 12, 2021

Abstract The 18 kDa translocator protein (TSPO) is a highly conserved located in the outer mitochondrial membrane. TSPO binding, as measured with positron emission tomography (PET), considered an vivo marker of neuroinflammation. Indeed, expression altered neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. In PET studies, signal often viewed microglial cell activity. However, there little evidence support microglia-specific expression. This review describes cellular sources functions animal models disease human health, central nervous system A discussion methods analysis quantification also presented. Overall, it appears that alterations their underpinnings, functional significance such depend on many factors, notably pathology or model under study, stage, involved brain regions. Thus, further studies are needed to fully determine how changes binding occur at level ultimate goal revealing potential therapeutic pathways.

Language: Английский

---

Microglia and Astrocyte Function and Communication: What Do We Know in Humans?

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Feb. 16, 2022

Microglia and astrocytes play essential roles in the central nervous system contributing to many functions including homeostasis, immune response, blood-brain barrier maintenance synaptic support. Evidence has emerged from experimental models of glial communication that microglia influence coordinate each other their effects on brain environment. However, due difference cells between humans rodents, it is confirm relevance these findings human brains. Here, we aim review current knowledge microglia-astrocyte crosstalk humans, exploring novel methodological techniques used health disease conditions. This will include an in-depth look at cell culture iPSCs,

Language: Английский

---

Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10572 - 10572

Published: Sept. 12, 2022

Alzheimer's disease (AD) is a progressive neurodegenerative disorder; it the most common cause of dementia and has no treatment. It characterized by two pathological hallmarks, extracellular deposits amyloid beta (Aβ) intraneuronal Neurofibrillary tangles (NFTs). Yet, those hallmarks do not explain full pathology seen with AD, suggesting involvement other mechanisms. Neuroinflammation could offer another explanation for progression disease. This review provides an overview recent advances on role immune cells' microglia astrocytes in neuroinflammation. In become reactive several mechanisms leading to release proinflammatory cytokines that further neuronal damage. We then provide updates neuroinflammation diagnostic markers investigational therapeutics currently clinical trials target

Language: Английский

---