scholarly journals TNF Production and Release from Microglia via Extracellular Vesicles: Impact on Brain Functions

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2145 ◽  
Author(s):  
Stefano Raffaele ◽  
Marta Lombardi ◽  
Claudia Verderio ◽  
Marta Fumagalli
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Neuroinflammatory Response ◽  
Brain Functions ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
Circuit Formation ◽  
Necrosis Factor

Tumor necrosis factor (TNF) is a pleiotropic cytokine powerfully influencing diverse processes of the central nervous system (CNS) under both physiological and pathological conditions. Here, we analyze current literature describing the molecular processes involved in TNF synthesis and release from microglia, the resident immune cells of the CNS and the main source of this cytokine both in brain development and neurodegenerative diseases. A special attention has been given to the unconventional vesicular pathway of TNF, based on the emerging role of microglia-derived extracellular vesicles (EVs) in the propagation of inflammatory signals and in mediating cell-to-cell communication. Moreover, we describe the contribution of microglial TNF in regulating important CNS functions, including the neuroinflammatory response following brain injury, the neuronal circuit formation and synaptic plasticity, and the processes of myelin damage and repair. Specifically, the available data on the functions mediated by microglial EVs carrying TNF have been scrutinized to gain insights on possible novel therapeutic strategies targeting TNF to foster CNS repair.

scholarly journals Platelet Extracellular Vesicles

2020 ◽  
Author(s):  
Florian Puhm ◽  
Eric Boilard ◽  
Kellie R. Machlus
Keyword(s):  
Bone Marrow ◽  
Synovial Fluid ◽  
Nucleic Acids ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Biological Processes ◽  
Vascular Integrity ◽  
Pathological Conditions ◽  
Broad Array

Extracellular vesicles (EVs) are a means of cell-to-cell communication and can facilitate the exchange of a broad array of molecules between adjacent or distant cells. Platelets are anucleate cells derived from megakaryocytes and are primarily known for their role in maintaining hemostasis and vascular integrity. Upon activation by a variety of agonists, platelets readily generate EVs, which were initially identified as procoagulant particles. However, as both platelets and their EVs are abundant in blood, the role of platelet EVs in hemostasis may be redundant. Moreover, findings have challenged the significance of platelet-derived EVs in coagulation. Looking beyond hemostasis, platelet EV cargo is incredibly diverse and can include lipids, proteins, nucleic acids, and organelles involved in numerous other biological processes. Furthermore, while platelets cannot cross tissue barriers, their EVs can enter lymph, bone marrow, and synovial fluid. This allows for the transfer of platelet-derived content to cellular recipients and organs inaccessible to platelets. This review highlights the importance of platelet-derived EVs in physiological and pathological conditions beyond hemostasis.

scholarly journals Emerging Roles of Extracellular Vesicles in the Central Nervous System: Physiology, Pathology, and Therapeutic Perspectives

2021 ◽  
Vol 15 ◽  
Author(s):  
Yadaly Gassama ◽  
Alexandre Favereaux
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
System Physiology ◽  
The Brain

Extracellular vesicles or EVs are secreted by most, if not all, eukaryote cell types and recaptured by neighboring or distant cells. Their cargo, composed of a vast diversity of proteins, lipids, and nucleic acids, supports the EVs’ inter-cellular communication. The role of EVs in many cellular processes is now well documented both in physiological and pathological conditions. In this review, we focus on the role of EVs in the central nervous system (CNS) in physiological as well as pathological conditions such as neurodegenerative diseases or brain cancers. We also discuss the future of EVs in clinical research, in particular, their value as biomarkers as well as innovative therapeutic agents. While an increasing number of studies reveal EV research as a promising field, progress in the standardization of protocols and innovation in analysis as well as in research tools is needed to make a breakthrough in our understanding of their impact in the pathophysiology of the brain.

scholarly journals The role of cytokines in modulating learning and memory and brain plasticity

2020 ◽  
Vol 4 ◽  
pp. 239821282097980
Author(s):  
Julie-Myrtille Bourgognon ◽  
Jonathan Cavanagh
Keyword(s):  
Learning And Memory ◽  
Brain Plasticity ◽  
Homeostatic Plasticity ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Factor Α ◽  
Peripheral Immune Cells ◽  
Necrosis Factor

Cytokines are proteins secreted in the central nervous system by neurons, microglia, astrocytes and infiltrating peripheral immune cells under physiological and pathological conditions. Over the last 20 years, a growing number of reports have investigated the effects of these molecules on brain plasticity. In this review, we describe how the key cytokines interleukin 1β, interleukin 6 and tumour necrosis factor α were found to support long-term plasticity and learning and memory processes in physiological conditions. In contrast, during inflammation where cytokines levels are elevated such as in models of brain injury or infection, depression or neurodegeneration, the effects of cytokines are mostly detrimental to memory mechanisms, associated behaviours and homeostatic plasticity.

scholarly journals Extracellular vesicles as modulators of cell-to-cell communication in the healthy and diseased brain

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130516 ◽  
Author(s):  
D. M. Pegtel ◽  
L. Peferoen ◽  
S. Amor
Keyword(s):  
Extracellular Vesicles ◽  
Messenger Rna ◽  
Potential Role ◽  
Cell Communication ◽  
Extracellular Rna ◽  
Anti Cancer ◽  
The Status ◽  
The Central Nervous System ◽  
Stressed Cells

Homeostasis relies heavily on effective cell-to-cell communication. In the central nervous system (CNS), probably more so than in other organs, such communication is crucial to support and protect neurons especially during ageing, as well as to control inflammation, remove debris and infectious agents. Emerging evidence indicates that extracellular vesicles (EVs) including endosome-derived exosomes and fragments of the cellular plasma membrane play a key role in intercellular communication by transporting messenger RNA, microRNA (miRNA) and proteins. In neurodegenerative diseases, secreted vesicles not only remove misfolded proteins, but also transfer aggregated proteins and prions and are thus thought to perpetuate diseases by ‘infecting’ neighbouring cells with these pathogenic proteins. Conversely, in other CNS disorders signals from stressed cells may help control inflammation and inhibit degeneration. EVs may also reflect the status of the CNS and are present in the cerebrospinal fluid indicating that exosomes may act as biomarkers of disease. That extracellular RNA and in particular miRNA, can be transferred by EV also indicates that these vesicles could be used as carriers to specifically target the CNS to deliver immune modulatory drugs, neuroprotective agents and anti-cancer drugs. Here, we discuss the recent evidence indicating the potential role of exosomes in neurological disorders and how knowledge of their biology may enable a Trojan-horse approach to deliver drugs into the CNS and treat neurodegenerative and other disorders of the CNS.

scholarly journals Monitoring and Modulating Inflammation-Associated Alterations in Synaptic Plasticity: Role of Brain Stimulation and the Blood–Brain Interface

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 359
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Andreas Vlachos
Keyword(s):  
Synaptic Plasticity ◽  
Brain Stimulation ◽  
Vascular Function ◽  
Neuropsychiatric Symptoms ◽  
Systemic Infection ◽  
Brain Functions ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System

Inflammation of the central nervous system can be triggered by endogenous and exogenous stimuli such as local or systemic infection, trauma, and stroke. In addition to neurodegeneration and cell death, alterations in physiological brain functions are often associated with neuroinflammation. Robust experimental evidence has demonstrated that inflammatory cytokines affect the ability of neurons to express plasticity. It has been well-established that inflammation-associated alterations in synaptic plasticity contribute to the development of neuropsychiatric symptoms. Nevertheless, diagnostic approaches and interventional strategies to restore inflammatory deficits in synaptic plasticity are limited. Here, we review recent findings on inflammation-associated alterations in synaptic plasticity and the potential role of the blood–brain interface, i.e., the blood–brain barrier, in modulating synaptic plasticity. Based on recent findings indicating that brain stimulation promotes plasticity and modulates vascular function, we argue that clinically employed non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, could be used for monitoring and modulating inflammation-induced alterations in synaptic plasticity.

scholarly journals From Exosome Glycobiology to Exosome Glycotechnology, the Role of Natural Occurring Polysaccharides

2021 ◽  
Vol 2 (2) ◽  
pp. 311-338
Author(s):  
Giulia Della Rosa ◽  
Clarissa Ruggeri ◽  
Alessandra Aloisi
Keyword(s):  
State Of The Art ◽  
Cell Communication ◽  
Pathological Conditions ◽  
New Findings ◽  
Cell Type Specific ◽  
New Perspective ◽  
And Function ◽  
And Personalized Medicine ◽  
Innate Ability

Exosomes (EXOs) are nano-sized informative shuttles acting as endogenous mediators of cell-to-cell communication. Their innate ability to target specific cells and deliver functional cargo is recently claimed as a promising theranostic strategy. The glycan profile, actively involved in the EXO biogenesis, release, sorting and function, is highly cell type-specific and frequently altered in pathological conditions. Therefore, the modulation of EXO glyco-composition has recently been considered an attractive tool in the design of novel therapeutics. In addition to the available approaches involving conventional glyco-engineering, soft technology is becoming more and more attractive for better exploiting EXO glycan tasks and optimizing EXO delivery platforms. This review, first, explores the main functions of EXO glycans and associates the potential implications of the reported new findings across the nanomedicine applications. The state-of-the-art of the last decade concerning the role of natural polysaccharides—as targeting molecules and in 3D soft structure manufacture matrices—is then analysed and highlighted, as an advancing EXO biofunction toolkit. The promising results, integrating the biopolymers area to the EXO-based bio-nanofabrication and bio-nanotechnology field, lay the foundation for further investigation and offer a new perspective in drug delivery and personalized medicine progress.

Microglia extracellular vesicles: focus on molecular composition and biological function

2021 ◽  
Vol 49 (4) ◽  
pp. 1779-1790 ◽  
Author(s):  
Lorenzo Ceccarelli ◽  
Chiara Giacomelli ◽  
Laura Marchetti ◽  
Claudia Martini
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Biological Function ◽  
Biological Effects ◽  
Genetic Material ◽  
Cell Communication ◽  
Molecular Composition ◽  
Cargo Proteins ◽  
A Cell ◽  
The Central Nervous System

Extracellular vesicles (EVs) are a heterogeneous family of cell-derived lipid bounded vesicles comprising exosomes and microvesicles. They are potentially produced by all types of cells and are used as a cell-to-cell communication method that allows protein, lipid, and genetic material exchange. Microglia cells produce a large number of EVs both in resting and activated conditions, in the latter case changing their production and related biological effects. Several actions of microglia in the central nervous system are ascribed to EVs, but the molecular mechanisms by which each effect occurs are still largely unknown. Conflicting functions have been ascribed to microglia-derived EVs starting from the neuronal support and ending with the propagation of inflammation and neurodegeneration, confirming the crucial role of these organelles in tuning brain homeostasis. Despite the increasing number of studies reported on microglia-EVs, there is also a lot of fragmentation in the knowledge on the mechanism at the basis of their production and modification of their cargo. In this review, a collection of literature data about the surface and cargo proteins and lipids as well as the miRNA content of EVs produced by microglial cells has been reported. A special highlight was given to the works in which the EV molecular composition is linked to a precise biological function.

scholarly journals The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Lattanzi ◽  
Cinzia Severini ◽  
Daniela Maftei ◽  
Luciano Saso ◽  
Aldo Badiani
Keyword(s):  
Pain Perception ◽  
G Protein Coupled Receptors ◽  
Cellular Processes ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Double Function ◽  
The Central Nervous System ◽  
G Protein Coupled

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

scholarly journals The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2316
Author(s):  
Lucia Catani ◽  
Michele Cavo ◽  
Francesca Palandri
Keyword(s):  
Extracellular Vesicles ◽  
Immune Escape ◽  
Myeloproliferative Neoplasms ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Driver Genes ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Patients Experience

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of bioactive molecules such as nucleic acids, proteins, metabolites and lipids. Growing interest is focused on EVs and their potential impact on the regulation of blood cancers. Overall, EVs have been suggested to orchestrate the complex interplay between tumor cells and the microenvironment with a pivotal role in “education” and “crafting” of the microenvironment by regulating angiogenesis, coagulation, immune escape and drug resistance of tumors. This review is focused on the role of EVs in MPN. Specifically, we will provide an overview of recent findings on the involvement of EVs in MPN pathogenesis and discuss opportunities for their potential application as diagnostic and prognostic biomarkers.

scholarly journals Efferent feedback enforces bilateral coupling of spontaneous activity in the developing auditory system

2020 ◽  
Author(s):  
Yixiang Wang ◽  
Maya Sanghvi ◽  
Alexandra Gribizis ◽  
Yueyi Zhang ◽  
Lei Song ◽  
...  
Keyword(s):  
Spontaneous Activity ◽  
Auditory System ◽  
Activity Patterns ◽  
Descending Pathways ◽  
Efferent System ◽  
Cholinergic Pathway ◽  
The Central Nervous System ◽  
Necessary And Sufficient ◽  
Circuit Formation

SummaryIn the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation before hearing onset. Effects of the evolving peripheral firing pattern on spontaneous activity in the central auditory system are not well understood. Here, we describe the wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the medial olivochlear (MOC) system. Knocking out the α9/α10 nicotinic acetylcholine receptor, a requisite part of the efferent cholinergic pathway, abolishes these bilateral correlations. Pharmacological and chemogenetic experiments confirm that the MOC system is necessary and sufficient to produce the bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, our results demonstrate how ascending and descending pathways collectively shape spontaneous activity patterns in the auditory system and reveal the essential role of the MOC efferent system in linking otherwise independent streams of bilateral spontaneous activity during the prehearing period.

Sign in / Sign up

Export Citation Format

Share Document