scholarly journals A Novel Tmem119-tdTomato Reporter Mouse Model for Studying Microglia in the Central Nervous System

2019 ◽  
Author(s):  
Chunsheng Ruan ◽  
Linlin Sun ◽  
Alexandra Kroshilina ◽  
Lien Beckers ◽  
Philip L. De Jager ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Mouse Model ◽  
Immune Cells ◽  
Exon 2 ◽  
Reporter Mouse ◽  
The Central Nervous System ◽  
Health And Disease

AbstractMicroglia are resident immune cells of the central nervous system (CNS). The exact role of microglia in the physiopathology of CNS disorders is not clear due to lack of tools to discriminate between CNS resident and infiltrated innate immune cells. Here, we present a novel reporter mouse model targeting a microglia-specific marker (TMEM119) for studying the function of microglia in health and disease. By placing a reporter cassette (GSG-3xFlag-P2A-tdTomato) between the coding sequence of exon 2 and 3’UTR of the Tmem119 gene using CRISPR/Cas9 technology, we generated a Tmem119-tdTomato knock-in mouse strain. Gene expression assay showed no difference of endogenous Tmem119 mRNA level in the CNS of Tmem119tdTomato/+ relative to control Wild-type mice. The cells expressing tdTomato-were recognized by immunofluorescence staining using commercially available anti-TMEM119 antibodies. Using immunofluorescence and flow cytometry techniques, tdTomato+ cells were detected throughout the CNS, but not in peripheral tissues of adult Tmem119tdTomato/+ mice. In addition, aging does not seem to influence TMEM119 expression as tdTomato+ cells were detectable in the CNS of older mice (300 and 540 days old). Further immunofluorescence characterization shows that the tdTomato+ cells were highly colocalized with Iba1+ cells (microglia and macrophages) in the brain, but not with NeuN- (neurons), GFAP- (astrocytes) or Olig2- (oligodendrocytes) labeled cells. Moreover, flow cytometry analysis of brain tissues of adult mice demonstrates that the majority of microglial CD45lowCD11b+ cells (96.6%) are tdTomato positive. Functionally, using a laser-induced injury model, we measured time-lapse activation of tdTomato-labeled microglia by transcranial two-photon microscopy in live Tmem119tdTomato/+ mice. Taken together, the Tmem119-tdTomato reporter mouse model will serve as a valuable tool to specifically study the role of microglia in health and disease.

scholarly journals Role of 5-HT7 receptors in the immune system in health and disease

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Alejandro Quintero-Villegas ◽  
Sergio Iván Valdés-Ferrer
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Immune System ◽  
Blood Platelets ◽  
Pain Tolerance ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
Health And Disease

AbstractIn mammalians, serotonin (5-HT) has critical roles in the central nervous system (CNS), including mood stability, pain tolerance, or sleep patterns. However, the vast majority of serotonin is produced by intestinal enterochromaffin cells of the gastrointestinal tract and circulating blood platelets, also acting outside of the CNS. Serotonin effects are mediated through its interaction with 5-HT receptors (5-HTRs), a superfamily with a repertoire of at least fourteen well-characterized members. 5-HT7 receptors are the last 5-HTR member to be identified, with well-defined functions in the nervous, gastrointestinal, and vascular systems. The effects of serotonin on the immune response are less well understood. Mast cells are known to produce serotonin, while T cells, dendritic cells, monocytes, macrophages and microglia express 5-HT7 receptor. Here, we review the known roles of 5-HT7 receptors in the immune system, as well as their potential therapeutic implication in inflammatory and immune-mediated disorders.

scholarly journals The Role of Microglia during West Nile Virus Infection of the Central Nervous System

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 485 ◽  
Author(s):  
Sarah Stonedahl ◽  
Penny Clarke ◽  
Kenneth L. Tyler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
West Nile Virus ◽  
Immune Cells ◽  
Neuronal Cell ◽  
The United States ◽  
Health Concern ◽  
West Nile ◽  
The Central Nervous System

Encephalitis resulting from viral infections is a major cause of hospitalization and death worldwide. West Nile Virus (WNV) is a substantial health concern as it is one of the leading causes of viral encephalitis in the United States today. WNV infiltrates the central nervous system (CNS), where it directly infects neurons and induces neuronal cell death, in part, via activation of caspase 3-mediated apoptosis. WNV infection also induces neuroinflammation characterized by activation of innate immune cells, including microglia and astrocytes, production of inflammatory cytokines, breakdown of the blood-brain barrier, and infiltration of peripheral leukocytes. Microglia are the resident immune cells of the brain and monitor the CNS for signs of injury or pathogens. Following infection with WNV, microglia exhibit a change in morphology consistent with activation and are associated with increased expression of proinflammatory cytokines. Recent research has focused on deciphering the role of microglia during WNV encephalitis. Microglia play a protective role during infections by limiting viral growth and reducing mortality in mice. However, it also appears that activated microglia are triggered by T cells to mediate synaptic elimination at late times during infection, which may contribute to long-term neurological deficits following a neuroinvasive WNV infection. This review will discuss the important role of microglia in the pathogenesis of a neuroinvasive WNV infection. Knowledge of the precise role of microglia during a WNV infection may lead to a greater ability to treat and manage WNV encephalitis.

scholarly journals Role of TREK-1 in Health and Disease, Focus on the Central Nervous System

2019 ◽  
Vol 10 ◽  
Author(s):  
Alaeddine Djillani ◽  
Jean Mazella ◽  
Catherine Heurteaux ◽  
Marc Borsotto
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Disease Focus

scholarly journals A novel Tmem119-tdTomato reporter mouse model for studying microglia in the central nervous system

2020 ◽  
Vol 83 ◽  
pp. 180-191 ◽  
Author(s):  
Chunsheng Ruan ◽  
Linlin Sun ◽  
Alexandra Kroshilina ◽  
Lien Beckers ◽  
Philip De Jager ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Reporter Mouse ◽  
The Central Nervous System

scholarly journals Role of the Extracellular Traps in Central Nervous System

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyan Wu ◽  
Hanhai Zeng ◽  
Lingxin Cai ◽  
Gao Chen
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Brain Barrier ◽  
Extracellular Traps ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Extracellular Trap

It has been reported that several immune cells can release chromatin and granular proteins into extracellular space in response to the stimulation, forming extracellular traps (ETs). The cells involved in the extracellular trap formation are recognized including neutropils, macrophages, basophils, eosinophils, and mast cells. With the development of research related to central nervous system, the role of ETs has been valued in neuroinflammation, blood–brain barrier, and other fields. Meanwhile, it has been found that microglial cells as the resident immune cells of the central nervous system can also release ETs, updating the original understanding. This review aims to clarify the role of the ETs in the central nervous system, especially in neuroinflammation and blood–brain barrier.

The gut-brain axis: microglia in the spotlight

Neuroforum ◽  
2019 ◽  
Vol 25 (3) ◽  
pp. 205-212 ◽  
Author(s):  
Charlotte Mezö ◽  
Omar Mossad ◽  
Daniel Erny ◽  
Thomas Blank
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Brain Functions ◽  
Microbiome Research ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Brain

Summary Microbiome research has grown significantly in the last decade, highlighting manifold implications of the microbiota to the host’s health. The gut microbiota is connected to the brain through several avenues that allow their interaction. Thus, recent studies have attemtpted to characterize these connections and enhance our understanding of the so called ‘gut-brain-axis’. Microglia, the central nervous system resident macrophages, are crucial for the proper development and maintenance of brain functions. As immune cells, they are in the spotlight for relaying signals between the microbiota and cells of the brain. In this review, we contemplate on interactions between the gut microbiota and microglia, and their influence on brain functions in health and disease.

scholarly journals MCAM/CD146 Signaling via PLCγ1 Leads to Activation of β1-Integrins in Memory T-Cells Resulting in Increased Brain Infiltration

2020 ◽  
Vol 11 ◽  
Author(s):  
Lisa Zondler ◽  
Sebastian Herich ◽  
Petra Kotte ◽  
Katharina Körner ◽  
Tilman Schneider-Hohendorf ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Immune Cells ◽  
Β1 Integrin ◽  
Integrin Activation ◽  
The Central Nervous System

Multiple sclerosis is a chronic auto-inflammatory disease of the central nervous system affecting patients worldwide. Neuroinflammation in multiple sclerosis is mainly driven by peripheral immune cells which invade the central nervous system and cause neurodegenerative inflammation. To enter the target tissue, immune cells have to overcome the endothelium and transmigrate into the tissue. Numerous molecules mediate this process and, as they determine the tissue invasiveness of immune cells, display great therapeutic potential. Melanoma cell adhesion molecule (MCAM) is a membrane-anchored glycoprotein expressed by a subset of T-cells and MCAM+ T-cells have been shown to contribute to neuroinflammation in multiple sclerosis. The role of the MCAM molecule for brain invasion, however, remained largely unknown. In order to investigate the role of the MCAM molecule on T-cells, we used different in vitro and in vivo assays, including ex vivo flow chambers, biochemistry and microscopy experiments of the mouse brain. We demonstrate that MCAM directly mediates adhesion and that the engagement of MCAM induces intracellular signaling leading to β1-integrin activation on human T-cells. Furthermore, we show that MCAM engagement triggers the phosphorylation of PLCγ1 which is required for integrin activation and thus amplification of the cellular adhesive potential. To confirm the physiological relevance of our findings in vivo, we demonstrate that MCAM plays an important role in T-cell recruitment into the mouse brain. In conclusion, our data demonstrate that MCAM expressed on T-cells acts as an adhesion molecule and a signaling receptor that may trigger β1-integrin activation via PLCγ1 upon engagement.

scholarly journals Multiple Sclerosis and the Blood-Central Nervous System Barrier

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Alan M. Palmer
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Immune Cells ◽  
Cannabinoid Receptors ◽  
Humanized Monoclonal Antibody ◽  
The Central Nervous System ◽  
Cns Side Effects ◽  
Cell Adhesion Molecule 1

The central nervous system (CNS) is isolated from the blood system by a physical barrier that contains efflux transporters and catabolic enzymes. This blood-CNS barrier (BCNSB) plays a pivotal role in the pathophysiology of multiple sclerosis (MS). It binds and anchors activated leukocytes to permit their movement across the BCNSB and into the CNS. Once there, these immune cells target particular self-epitopes and initiate a cascade of neuroinflammation, which leads to the breakdown of the BCNSB and the formation of perivascular plaques, one of the hallmarks of MS. Immunomodulatory drugs for MS are either biologics or small molecules, with only the latter having the capacity to cross the BCNSB and thus have a propensity to cause CNS side effects. However, BCNSB penetration is a desirable feature of MS drugs that have molecular targets within the CNS. These are nabiximols and dalfampridine, which target cannabinoid receptors and potassium channels, respectively. Vascular cell adhesion molecule-1, present on endothelial cells of the BCNSB, also serves as a drug discovery target since it interacts with α4-β1-integrin on leucocytes. The MS drug natalizumab, a humanized monoclonal antibody against α4-β1-integrin, blocks this interaction and thus reduces the movement of immune cells into the CNS. This paper further elaborates on the role of the BCNSB in the pathophysiology and pharmacotherapy of MS.

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