scholarly journals Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

2016 ◽  
Vol 41 (5) ◽  
pp. E10 ◽  
Author(s):  
Jason K. Karimy ◽  
Daniel Duran ◽  
Jamie K. Hu ◽  
Charuta Gavankar ◽  
Jonathan R. Gaillard ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Molecular Mechanisms ◽  
Human Genetics ◽  
Past Century ◽  
Choroid Plexus Epithelium ◽  
Hydrodynamic Models ◽  
Molecular Physiology ◽  
Pediatric Hydrocephalus ◽  
Shunt Dependence

Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

scholarly journals The Neurobiology of Selenium: Looking Back and to the Future

2021 ◽  
Vol 15 ◽  
Author(s):  
Ulrich Schweizer ◽  
Simon Bohleber ◽  
Wenchao Zhao ◽  
Noelia Fradejas-Villar
Keyword(s):  
Cell Biology ◽  
Molecular Mechanisms ◽  
Human Genetics ◽  
Epileptic Seizures ◽  
Cell Types ◽  
Mammalian Brain ◽  
The Individual ◽  
The Brain ◽  
Looking Back

Eighteen years ago, unexpected epileptic seizures in Selenop-knockout mice pointed to a potentially novel, possibly underestimated, and previously difficult to study role of selenium (Se) in the mammalian brain. This mouse model was the key to open the field of molecular mechanisms, i.e., to delineate the roles of selenium and individual selenoproteins in the brain, and answer specific questions like: how does Se enter the brain; which processes and which cell types are dependent on selenoproteins; and, what are the individual roles of selenoproteins in the brain? Many of these questions have been answered and much progress is being made to fill remaining gaps. Mouse and human genetics have together boosted the field tremendously, in addition to traditional biochemistry and cell biology. As always, new questions have become apparent or more pressing with solving older questions. We will briefly summarize what we know about selenoproteins in the human brain, glance over to the mouse as a useful model, and then discuss new questions and directions the field might take in the next 18 years.

scholarly journals Electrophysiological and Molecular Mechanisms of Sinoatrial Node Mechanosensitivity

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniel Turner ◽  
Chen Kang ◽  
Pietro Mesirca ◽  
Juan Hong ◽  
Matteo E. Mangoni ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Ion Channels ◽  
Chloride Channels ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Sinoatrial Node ◽  
Receptor Potential ◽  
Past Century ◽  
Transient Receptor

The understanding of the electrophysiological mechanisms that underlie mechanosensitivity of the sinoatrial node (SAN), the primary pacemaker of the heart, has been evolving over the past century. The heart is constantly exposed to a dynamic mechanical environment; as such, the SAN has numerous canonical and emerging mechanosensitive ion channels and signaling pathways that govern its ability to respond to both fast (within second or on beat-to-beat manner) and slow (minutes) timescales. This review summarizes the effects of mechanical loading on the SAN activity and reviews putative candidates, including fast mechanoactivated channels (Piezo, TREK, and BK) and slow mechanoresponsive ion channels [including volume-regulated chloride channels and transient receptor potential (TRP)], as well as the components of mechanochemical signal transduction, which may contribute to SAN mechanosensitivity. Furthermore, we examine the structural foundation for both mechano-electrical and mechanochemical signal transduction and discuss the role of specialized membrane nanodomains, namely, caveolae, in mechanical regulation of both membrane and calcium clock components of the so-called coupled-clock pacemaker system responsible for SAN automaticity. Finally, we emphasize how these mechanically activated changes contribute to the pathophysiology of SAN dysfunction and discuss controversial areas necessitating future investigations. Though the exact mechanisms of SAN mechanosensitivity are currently unknown, identification of such components, their impact into SAN pacemaking, and pathological remodeling may provide new therapeutic targets for the treatment of SAN dysfunction and associated rhythm abnormalities.

Role of choroid plexus epithelium in the removal of valproic acid from the central nervous system

1995 ◽  
Vol 20 (3) ◽  
pp. 185-192 ◽  
Author(s):  
Kimberly D.K. Adkison ◽  
Alan A. Artru ◽  
Karen M. Powers ◽  
David Nochlin ◽  
Danny D. Shen
Keyword(s):  
Central Nervous System ◽  
Valproic Acid ◽  
Nervous System ◽  
Choroid Plexus ◽  
Choroid Plexus Epithelium ◽  
The Central Nervous System

scholarly journals NLRP3 inflammasome-mediated cerebrospinal fluid hypersecretion in choroid plexus contributes to hydrocephalus after hemorrhage

2020 ◽  
Author(s):  
Zhaoqi Zhang ◽  
Qiang Tan ◽  
Peiwen Guo ◽  
Zhengcai Jia ◽  
Xin Liu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Strategy ◽  
Autologous Blood ◽  
Major Protein ◽  
Choroid Plexus Epithelium ◽  
Barrier Integrity ◽  
The Relationship

Abstract BackgroundHydrocephalus is a severe complication of intracerebral hemorrhage with ventricular extension (ICH-IVH). The choroid plexus epithelium plays an important role in cerebrospinal fluid (CSF) secretion and constitutes blood-CSF barrier adjusting brain–immune system interface. NLRP3 inflammasome is a key component of the innate system which promotes neuroinflammation. However, the role of NLRP3 inflammasome in the pathogenesis of hydrocephalus after hemorrhage has not been investigated.MethodsHydrocephalus after ICH-IVH rat model was accomplished by autologous blood infusion. Then, we investigated the relationship between NLRP3 inflammasome and CSF hypersecretion in choroid plexus.ResultsThe NLRP3 inflammasome activated and CSF hypersecretion in choroid plexus epithelium were found after ICH-IVH. NLRP3 inhibition with MCC950 decreased CSF secretion, ventricles dilation and attenuated neurofunction deficits after ICH-IVH. In addition, MCC950 decreased NKCC1 phosphorylation which was the major protein adjusting CSF secretion and improved blood-CSF barrier integrity after ICH-IVH.ConclusionsThis study demonstrates that NLRP3 inflammasome mediated CSF hypersecretion by influencing NKCC1 phosphorylation in choroid plexus epithelium plays an important role in the pathogenesis of hydrocephalus after hemorrhage and provides a new therapeutic strategy.

scholarly journals Gelsolin Restores Aβ-Induced Alterations in Choroid Plexus Epithelium

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Teo Vargas ◽  
Desiree Antequera ◽  
Cristina Ugalde ◽  
Carlos Spuch ◽  
Eva Carro
Keyword(s):  
Choroid Plexus ◽  
Molecular Mechanisms ◽  
Prophylactic Treatment ◽  
Senile Plaques ◽  
Choroid Plexus Epithelium ◽  
Amyloid Deposits ◽  
Cytoskeletal Disruption ◽  
The Brain ◽  
Epithelial Cell Death ◽  
Cerebrovascular Amyloid

Histologically, Alzheimer's disease (AD) is characterized by senile plaques and cerebrovascular amyloid deposits. In previous studies we demonstrated that in AD patients, amyloid-β(Aβ) peptide also accumulates in choroid plexus, and that this process is associated with mitochondrial dysfunction and epithelial cell death. However, the molecular mechanisms underlying Aβaccumulation at the choroid plexus epithelium remain unclear. Aβclearance, from the brain to the blood, involves Aβcarrier proteins that bind to megalin, including gelsolin, a protein produced specifically by the choroid plexus epithelial cells. In this study, we show that treatment with gelsolin reduces Aβ-induced cytoskeletal disruption of blood-cerebrospinal fluid (CSF) barrier at the choroid plexus. Additionally, our results demonstrate that gelsolin plays an important role in decreasing Aβ-induced cytotoxicity by inhibiting nitric oxide production and apoptotic mitochondrial changes. Taken together, these findings make gelsolin an appealing tool for the prophylactic treatment of AD.

S100A1: a novel inotropic regulator of cardiac performance. Transition from molecular physiology to pathophysiological relevance

2007 ◽  
Vol 293 (2) ◽  
pp. R568-R577 ◽  
Author(s):  
Patrick Most ◽  
Andrew Remppis ◽  
Sven T. Pleger ◽  
Hugo A. Katus ◽  
Walter J. Koch
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Molecular Physiology ◽  
Ef Hand ◽  
Physiological Regulator ◽  
Function Relationship ◽  
Relationship Of ◽  
Considerable Body ◽  
Shed Light

Here we review the considerable body of evidence that has accumulated to support the notion of S100A1, a cardiac-specific Ca2+-sensor protein of the EF-hand type, as a physiological regulator of excitation-contraction coupling and inotropic reserve mechanisms in the mammalian heart. In particular, molecular mechanisms will be discussed conveying the Ca2+-dependent inotropic actions of S100A1 protein in cardiomyocytes occurring independently of β-adrenergic signaling. Moreover, we will shed light on the molecular structure-function relationship of S100A1 with its cardiac target proteins at the sarcoplasmic reticulum, the sarcomere, and the mitochondria. Furthermore, pathophysiological consequences of disturbed S100A1 protein expression on altered Ca2+handling and intertwined systems in failing myocardium will be highlighted. Subsequently, therapeutic options by means of genetic manipulation of cardiac S100A1 expression will be discussed, aiming to complete our current understanding of the role of S100A1 in diseased myocardium.

Organization of tight junctions in the choroid plexus epithelium

1978 ◽  
Vol 36 (2) ◽  
pp. 336-337
Author(s):  
B. Van Deurs ◽  
J. K. Koehler
Keyword(s):  
Choroid Plexus ◽  
Present Report ◽  
Freeze Fracture ◽  
Barrier Properties ◽  
Cell Junctions ◽  
Structural Basis ◽  
Apical Surface ◽  
Choroid Plexus Epithelium ◽  
Solid Nitrogen ◽  
Special Composition

The choroid plexus epithelium constitutes a blood-cerebrospinal fluid (CSF) barrier, and is involved in regulation of the special composition of the CSF. The epithelium is provided with an ouabain-sensitive Na/K-pump located at the apical surface, actively pumping ions into the CSF. The choroid plexus epithelium has been described as “leaky” with a low transepithelial resistance, and a passive transepithelial flux following a paracellular route (intercellular spaces and cell junctions) also takes place. The present report describes the structural basis for these “barrier” properties of the choroid plexus epithelium as revealed by freeze fracture.Choroid plexus from the lateral, third and fourth ventricles of rats were used. The tissue was fixed in glutaraldehyde and stored in 30% glycerol. Freezing was performed either in liquid nitrogen-cooled Freon 22, or directly in a mixture of liquid and solid nitrogen prepared in a special vacuum chamber. The latter method was always used, and considered necessary, when preparations of complementary (double) replicas were made.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

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