scholarly journals Resurgent Sodium Current in Neurons of the Cerebral Cortex

2021 ◽  
Vol 15 ◽  
Author(s):  
Giulia Quattrocolo ◽  
Keagan Dunville ◽  
Maximiliano José Nigro
Keyword(s):  
Cerebral Cortex ◽  
Current Knowledge ◽  
Sodium Current ◽  
Basic Research ◽  
Cell Types ◽  
Neuronal Types ◽  
And Function ◽  
Cerebellar Purkinje Neurons ◽  
Different Cell Types ◽  
Resurgent Sodium Current

In the late ’90, Dr. Indira Raman, at the time a postdoctoral fellow with Dr. Bruce Bean, at Harvard University, identified a new type of sodium current, flowing through the channels that reopens when the membrane is repolarized. This current, called “resurgent Sodium current,” was originally identified in cerebellar Purkinje neurons and has now been confirmed in around 20 different neuronal types. Since moving to Northwestern University in 1999 to establish her own research group, Dr. Raman has dedicated great efforts in identifying the mechanisms supporting the resurgent Sodium current and how its biophysical properties shape the firing of the different cell types. Her work has impacted greatly the field of cellular neurophysiology, from basic research to translation neuroscience. In fact, alterations in the resurgent sodium currents have been observed in several neuropathologies, from Huntington’s disease to epilepsy. In this Perspective we will focus on the current knowledge on the expression and function of the resurgent Sodium current in neurons of the cerebral cortex and hippocampus. We will also briefly highlight the role of Dr. Raman’s as teacher and mentor, not only for her pupils, but for the whole scientific community.

scholarly journals Neonatal Fc receptor (FcRn) – not only transporter of maternal IgG

2018 ◽  
Vol 72 ◽  
pp. 701-727
Author(s):  
Joanna E. Mikulska
Keyword(s):  
Mhc Class I ◽  
Current Knowledge ◽  
Cell Types ◽  
Fc Receptor ◽  
Class I ◽  
Neonatal Fc Receptor ◽  
The Status ◽  
And Function ◽  
Different Cell Types ◽  
Maternal Igg

The neonatal Fc receptor, (FcRn) is a transmembrane, heterodimeric glycoprotein with a structure similar to MHC class I molecules. In contrast to MHC class I antigens, FcRn does not bind to peptides (antigens) but interacts with the Fc fragment of IgG and albumin. The FcRn-IgG interaction as well as the FcRn-albumin interaction occur at acidic pH (optimally at pH 5.0-6.5) but not in physiological environment. These two ligands bind to distinct binding sites on the receptor molecule and by different mechanisms. Now, it is known that the expression of FcRn is not restricted to sites involved in the transport of maternal IgG, and this receptor is not responsible only for transfer the passive immunity from mother to the offspring. But FcRn has a much broader range of expression and function, throughout life and in many different cell types and tissues of humans and animals. This review summarizes the status of our knowledge on the expression, interaction with ligands and functions of the neonatal Fc receptor. This article shows also the possibilities of utilizing a current knowledge on FcRn for therapeutic purposes.

Versatile roles for myosin Va in dense core vesicle biogenesis and function

2010 ◽  
Vol 38 (1) ◽  
pp. 199-204 ◽  
Author(s):  
Tanja Kögel ◽  
Claudia Margarethe Bittins ◽  
Rüdiger Rudolf ◽  
Hans-Hermann Gerdes
Keyword(s):  
Actin Filaments ◽  
Current Knowledge ◽  
Cell Types ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Experimental Systems ◽  
Vesicle Biogenesis ◽  
Myosin Va ◽  
And Function ◽  
Different Cell Types

The motor protein myosin Va is involved in multiple successive steps in the development of dense-core vesicles, such as in the membrane remodelling during their maturation, their transport along actin filaments and the regulation of their exocytosis. In the present paper, we summarize the current knowledge on the roles of myosin Va in the different steps of dense-core vesicle biogenesis and exocytosis, and compare findings obtained from different cell types and experimental systems.

scholarly journals Integration, coincidence detection and resonance in networks of spiking neurons expressing Gamma oscillations and asynchronous states

2021 ◽  
Vol 17 (9) ◽  
pp. e1009416
Author(s):  
Eduarda Susin ◽  
Alain Destexhe
Keyword(s):  
Cerebral Cortex ◽  
Pyramidal Neurons ◽  
Network Models ◽  
Cell Types ◽  
Gamma Oscillations ◽  
Coincidence Detection ◽  
Biophysical Models ◽  
Firing Mode ◽  
Different Cell Types ◽  
External Stimuli

Gamma oscillations are widely seen in the awake and sleeping cerebral cortex, but the exact role of these oscillations is still debated. Here, we used biophysical models to examine how Gamma oscillations may participate to the processing of afferent stimuli. We constructed conductance-based network models of Gamma oscillations, based on different cell types found in cerebral cortex. The models were adjusted to extracellular unit recordings in humans, where Gamma oscillations always coexist with the asynchronous firing mode. We considered three different mechanisms to generate Gamma, first a mechanism based on the interaction between pyramidal neurons and interneurons (PING), second a mechanism in which Gamma is generated by interneuron networks (ING) and third, a mechanism which relies on Gamma oscillations generated by pacemaker chattering neurons (CHING). We find that all three mechanisms generate features consistent with human recordings, but that the ING mechanism is most consistent with the firing rate change inside Gamma bursts seen in the human data. We next evaluated the responsiveness and resonant properties of these networks, contrasting Gamma oscillations with the asynchronous mode. We find that for both slowly-varying stimuli and precisely-timed stimuli, the responsiveness is generally lower during Gamma compared to asynchronous states, while resonant properties are similar around the Gamma band. We could not find conditions where Gamma oscillations were more responsive. We therefore predict that asynchronous states provide the highest responsiveness to external stimuli, while Gamma oscillations tend to overall diminish responsiveness.

scholarly journals Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons

2021 ◽  
Vol 14 ◽  
Author(s):  
Elise Liu ◽  
Léa Karpf ◽  
Delphine Bohl
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Immune System ◽  
Frontotemporal Dementia ◽  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Cell Types ◽  
Induced Pluripotent ◽  
Different Cell Types ◽  
Lateral Sclerosis

Inflammation is a shared hallmark between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). For long, studies were conducted on tissues of post-mortem patients and neuroinflammation was thought to be only bystander result of the disease with the immune system reacting to dying neurons. In the last two decades, thanks to improving technologies, the identification of causal genes and the development of new tools and models, the involvement of inflammation has emerged as a potential driver of the diseases and evolved as a new area of intense research. In this review, we present the current knowledge about neuroinflammation in ALS, ALS-FTD, and FTD patients and animal models and we discuss reasons of failures linked to therapeutic trials with immunomodulator drugs. Then we present the induced pluripotent stem cell (iPSC) technology and its interest as a new tool to have a better immunopathological comprehension of both diseases in a human context. The iPSC technology giving the unique opportunity to study cells across differentiation and maturation times, brings the hope to shed light on the different mechanisms linking neurodegeneration and activation of the immune system. Protocols available to differentiate iPSC into different immune cell types are presented. Finally, we discuss the interest in studying monocultures of iPS-derived immune cells, co-cultures with neurons and 3D cultures with different cell types, as more integrated cellular approaches. The hope is that the future work with human iPS-derived cells helps not only to identify disease-specific defects in the different cell types but also to decipher the synergistic effects between neurons and immune cells. These new cellular tools could help to find new therapeutic approaches for all patients with ALS, ALS-FTD, and FTD.

Implications of microRNAs in the pathogenesis of atherosclerosis and prospects for therapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Armita Mahdavi Gorabi ◽  
Mohsen Ghanbari ◽  
Thozhukat Sathyapalan ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Immune Cell ◽  
Cholesterol Metabolism ◽  
Current Knowledge ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Fine Tuning ◽  
Lipid Uptake ◽  
Atherosclerosis Development ◽  
Signaling Receptors ◽  
Different Cell Types

MicroRNAs (miRNAs) are non-coding RNAs containing around 22 nucleotides, which are expressed in vertebrates and plants. They act as posttranscriptional gene expression regulators, fine-tuning various biological processes in different cell types. There is emerging evidence on their role in different stages of atherosclerosis. In addition to regulating the inflammatory cells involved in atherosclerosis, miRNAs play fundamental roles in the pathophysiology of atherosclerosis such as endothelial cell (EC) dysfunction, the aberrant function of the vascular smooth muscle cell (VSMC) and cholesterol metabolism. Moreover, miRNAs participate in several pathogenic pathways of atherosclerotic plaque development, including their effects on immune cell signaling receptors and lipid uptake. In this study, we review our current knowledge of the regulatory role of miRNAs in various pathogenic pathways underlying atherosclerosis development and also outline potential clinical applications of miRNAs in atherosclerosis.

Acute-phase responses and adipocytokines

2013 ◽  
pp. 424-430
Author(s):  
Elena Neumann ◽  
Klaus Frommer ◽  
Ulf Müller-Ladner
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Chronic Inflammation ◽  
Acute Phase ◽  
Rheumatic Diseases ◽  
Innate Immune System ◽  
Current Knowledge ◽  
Cell Types ◽  
Bioactive Substances ◽  
Different Cell Types

Adipokines, also called adipocytokines, are highly bioactive substances mainly expressed by adipose tissue. In addition to adipocytes, different cell types resident in various tissues produce adipokines under pathophysiological conditions. Adipokines include a growing number of pluripotent molecules such as adiponectin, resistin, leptin, and visfatin. Since distinct effects of adipokines on inflammation have been described, their influence on the (innate) immune system has been investigated in rheumatology, gastroenterology, and endocrinology. This review gives an overview on the current knowledge about the influence which adipokines have on the immune system and chronic inflammation in rheumatic diseases.

scholarly journals A systems perspective of heterocellular signaling

2018 ◽  
Vol 62 (4) ◽  
pp. 607-617 ◽  
Author(s):  
Alan Wells ◽  
H. Steven Wiley
Keyword(s):  
Cell Types ◽  
Regulatory Processes ◽  
Technical Developments ◽  
Building Models ◽  
Realistic Description ◽  
Multiple Cell ◽  
Solid Foundation ◽  
And Function ◽  
Multicellular Organisms ◽  
Different Cell Types

Signal exchange between different cell types is essential for development and function of multicellular organisms, and its dysregulation is causal in many diseases. Unfortunately, most cell-signaling work has employed single cell types grown under conditions unrelated to their native context. Recent technical developments have started to provide the tools needed to follow signaling between multiple cell types, but gaps in the information they provide have limited their usefulness in building realistic models of heterocellular signaling. Currently, only targeted assays have the necessary sensitivity, selectivity, and spatial resolution to usefully probe heterocellular signaling processes, but these are best used to test specific, mechanistic models. Decades of systems biology research with monocultures has provided a solid foundation for building models of heterocellular signaling, but current models lack a realistic description of regulated proteolysis and the feedback processes triggered within and between cells. Identification and understanding of key regulatory processes in the extracellular environment and of recursive signaling patterns between cells will be essential to building predictive models of heterocellular systems.

scholarly journals Mitochondrial Heterogeneity in the Brain at the Cellular Level

1998 ◽  
Vol 18 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Ursula Sonnewald ◽  
Leif Hertz ◽  
Arne Schousboe
Keyword(s):  
Amino Acid ◽  
Current Knowledge ◽  
Cell Types ◽  
Cellular Level ◽  
Mitochondrial Structure ◽  
Cell Type Specific ◽  
Mitochondrial Heterogeneity ◽  
Specific Tissue ◽  
And Function ◽  
The Brain

Classically, compartmentation of glutamate metabolism in the brain is associated with the fact that neurons and glia exhibit distinct differences with regard to metabolism of this amino acid. The recent use of 13C-labeled compounds to study this metabolism in conjunction with the availability of cell type-specific tissue culture modes has led to the notion that such compartmentation may even be present in individual cell types, neurons as well as glia. To better understand and explain this, it is proposed that mitochondrial heterogeneity may exist resulting in tricarboxylic acid cycles with different properties regarding cycling rates and ratio as well as coupling to amino acid biosynthesis, primarily involving glutamate and aspartate. These hypotheses are evaluated in the light of current knowledge about mitochondrial structure and function.

scholarly journals The story of the fibrin(ogen) αC-domains: evolution of our view on their structure and interactions

2021 ◽  
Author(s):  
Leonid Medved ◽  
John W Weisel
Keyword(s):  
Binding Sites ◽  
Current Knowledge ◽  
Optical Trap ◽  
Cell Types ◽  
Ordered Structures ◽  
Multiple Binding Sites ◽  
New Information ◽  
Multiple Binding ◽  
And Function ◽  
Fibrinogen Molecule

Although much has been established concerning the overall structure and function of fibrinogen, much less has been known about its two αC regions, each consisting of an αC-connector and αC-domain, but new information has been accumulating. This review summarizes the state of our current knowledge of the structure and interactions of fibrinogen’s αC regions. A series of studies with isolated αC regions and their fragments demonstrated that the αC-domain forms compact ordered structures consisting of N- and C-terminal sub-domains including β sheets and suggested that the αC-connector has a poly(L-proline) type II structure. Functionally, the αC-domains interact intramolecularly with each other and with the central region of the molecule, first demonstrated by electron microscopy and then quantified by optical trap force spectroscopy. Upon conversion of fibrinogen into fibrin, the αC-domains switch from intra- to intermolecular interactions to form ordered αC polymers. The formation of αC polymers occurs mainly through the homophilic interaction between the N-terminal sub-domains; interaction between the C-terminal sub-domains and the αC-connectors also contributes to this process. Considerable evidence supports the idea that the αC-regions accelerate fibrin polymerization and affect the final structure of fibrin clots. The interactions between αC-regions are important for the mechanical properties of clots, increasing their stiffness and extensibility. Conversion of fibrinogen into fibrin results in exposure of multiple binding sites in its αC regions, providing interaction of fibrin with different proteins and cell types during hemostasis and wound healing. This heretofore mysterious part of the fibrinogen molecule is finally giving up its secrets.

scholarly journals Plasticity of vascular resident mesenchymal stromal cells during vascular remodeling

2019 ◽  
Vol 1 (1) ◽  
pp. H67-H73
Author(s):  
Xuechong Hong ◽  
Wenduo Gu
Keyword(s):  
Vascular Remodeling ◽  
Current Knowledge ◽  
Vascular Diseases ◽  
Cell Types ◽  
Vascular Wall ◽  
Pathological Process ◽  
Therapeutic Approaches ◽  
And Behavior ◽  
Different Cell Types ◽  
Stromal Stem Cells

Vascular remodeling is a complex and dynamic pathological process engaging many different cell types that reside within the vasculature. Mesenchymal stromal/stem cells (MSCs) refer to a heterogeneous cell population with the plasticity to differentiate toward multiple mesodermal lineages. Various types of MSC have been identified within the vascular wall that actively contribute to the vascular remodeling process such as atherosclerosis. With the advances of genetic mouse models, recent findings demonstrated the crucial roles of MSCs in the progression of vascular diseases. This review aims to provide an overview on the current knowledge of the characteristics and behavior of vascular resident MSCs under quiescence and remodeling conditions, which may lead to the development of novel therapeutic approaches for cardiovascular diseases.

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