scholarly journals Synchronization of mammalian motile cilia in the brain with hydrodynamic forces

2019 ◽  
Author(s):  
Nicola Pellicciotta ◽  
Evelyn Hamilton ◽  
Jurij Kotar ◽  
Marion Faucourt ◽  
Nathalie Degehyr ◽  
...  
Keyword(s):  
Mechanistic Model ◽  
Hydrodynamic Forces ◽  
Coordination Mechanism ◽  
Mammalian Brain ◽  
Similar Frequency ◽  
Multiciliated Cells ◽  
Motile Cilia ◽  
External Flows ◽  
The Brain

Motile cilia are widespread across the animal and plant kingdoms, displaying complex collective dynamics central to their physiology. Their coordination mechanism is not generally understood, with pre-vious work mainly focusing on algae and protists. We study here the synchronization of cilia beat in multiciliated cells from brain ven-tricles. The response to controlled oscillatory external flows shows that strong flows at a similar frequency to the actively beating cilia can entrain cilia oscillations. We find that the hydrodynamic forces required for this entrainment strongly depend on the number of cilia per cell. Cells with few cilia (up to five) can be entrained at flows comparable to the cilia-driven flows reported in vivo. Simulations of a minimal model of cilia interacting hydrodynamically show the same trends observed in cilia. Our results suggest that hydrody-namic forces between cilia are sufficient to be the mechanism behind the synchronization of mammalian brain cilia dynamics.Significance StatementIt is shown experimentally, and also reproducing key qualitative results in a minimal mechanistic model simulated numerically, that in the motile cilia of the brain hydrodynamic forces of the magnitude that cilia themselves can generate are sufficient to establish the coordination of dynamics which is so crucial phys-iologically. This is the first experiment of its kind on multicilated cells, the key result is the unexpected importance of cilia num-ber per cell, with cells with fewer cilia much more susceptible to external flows. This finding changes the way in which we think about the question of collective cilia beating - it is not correct to simply examine isolated cilia and draw conclusions about the behaviour of cilia assemblies in multiciliated cells.

scholarly journals Entrainment of mammalian motile cilia in the brain with hydrodynamic forces

2020 ◽  
Vol 117 (15) ◽  
pp. 8315-8325 ◽  
Author(s):  
Nicola Pellicciotta ◽  
Evelyn Hamilton ◽  
Jurij Kotar ◽  
Marion Faucourt ◽  
Nathalie Delgehyr ◽  
...  
Keyword(s):  
Hydrodynamic Forces ◽  
Coordination Mechanism ◽  
Similar Frequency ◽  
Brain Ventricles ◽  
Flagellar Beat ◽  
Multiciliated Cells ◽  
Hydrodynamic Screening ◽  
Motile Cilia ◽  
External Flows ◽  
The Brain

Motile cilia are widespread across the animal and plant kingdoms, displaying complex collective dynamics central to their physiology. Their coordination mechanism is not generally understood, with previous work mainly focusing on algae and protists. We study here the entrainment of cilia beat in multiciliated cells from brain ventricles. The response to controlled oscillatory external flows shows that flows at a similar frequency to the actively beating cilia can entrain cilia oscillations. We find that the hydrodynamic forces required for this entrainment strongly depend on the number of cilia per cell. Cells with few cilia (up to five) can be entrained at flows comparable to cilia-driven flows, in contrast with what was recently observed in Chlamydomonas. Experimental trends are quantitatively described by a model that accounts for hydrodynamic screening of packed cilia and the chemomechanical energy efficiency of the flagellar beat. Simulations of a minimal model of cilia interacting hydrodynamically show the same trends observed in cilia.

scholarly journals SARS-CoV-2 infection induces the dedifferentiation of multiciliated cells and impairs mucociliary clearance

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rémy Robinot ◽  
Mathieu Hubert ◽  
Guilherme Dias de Melo ◽  
Françoise Lazarini ◽  
Timothée Bruel ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Mucociliary Clearance ◽  
Bronchial Epithelium ◽  
Lung Parenchyma ◽  
Ultrastructural Level ◽  
Epithelial Barrier Function ◽  
Multiciliated Cells ◽  
Motile Cilia ◽  
Cell Mobilization

AbstractUnderstanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. Here we examine the functional and structural consequences of SARS-CoV-2 infection in a reconstructed human bronchial epithelium model. SARS-CoV-2 replication causes a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remains limited. Rather, SARS-CoV-2 replication leads to a rapid loss of the ciliary layer, characterized at the ultrastructural level by axoneme loss and misorientation of remaining basal bodies. Downregulation of the master regulator of ciliogenesis Foxj1 occurs prior to extensive cilia loss, implicating this transcription factor in the dedifferentiation of ciliated cells. Motile cilia function is compromised by SARS-CoV-2 infection, as measured in a mucociliary clearance assay. Epithelial defense mechanisms, including basal cell mobilization and interferon-lambda induction, ramp up only after the initiation of cilia damage. Analysis of SARS-CoV-2 infection in Syrian hamsters further demonstrates the loss of motile cilia in vivo. This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma.

scholarly journals A Gustotopic Map of Taste Qualities in the Mammalian Brain

Science ◽  
2011 ◽  
Vol 333 (6047) ◽  
pp. 1262-1266 ◽  
Author(s):  
Xiaoke Chen ◽  
Mariano Gabitto ◽  
Yueqing Peng ◽  
Nicholas J. P. Ryba ◽  
Charles S. Zuker
Keyword(s):  
Taste Receptor ◽  
Taste Quality ◽  
Mammalian Brain ◽  
Taste System ◽  
Two Photon ◽  
Central Representation ◽  
The Brain ◽  
Cortical Field ◽  
Taste Coding

The taste system is one of our fundamental senses, responsible for detecting and responding to sweet, bitter, umami, salty, and sour stimuli. In the tongue, the five basic tastes are mediated by separate classes of taste receptor cells each finely tuned to a single taste quality. We explored the logic of taste coding in the brain by examining how sweet, bitter, umami, and salty qualities are represented in the primary taste cortex of mice. We used in vivo two-photon calcium imaging to demonstrate topographic segregation in the functional architecture of the gustatory cortex. Each taste quality is represented in its own separate cortical field, revealing the existence of a gustotopic map in the brain. These results expose the basic logic for the central representation of taste.

Glutamic Acid and Glucose As Substrates for Mammalian Brain

1951 ◽  
Vol 97 (409) ◽  
pp. 674-680 ◽  
Author(s):  
H. McIlwain
Keyword(s):  
Glutamic Acid ◽  
Functional Activity ◽  
Metabolic Effects ◽  
Mammalian Brain ◽  
The Past ◽  
The Brain

Effects of substances on the respiration of unstimulated portions of mammalian brain have been used in the past as aids to understanding or suggesting their actions on the brain in vivo. The present paper gives data with respect to glucose and glutamic acid, which show some of the limitations of such interpretations. It also describes the application of new experimental means of examining the metabolic effects of added substances in relation to the functional activity of the brain.

scholarly journals Lactate-mediated glia-neuronal signalling in the mammalian brain

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
F. Tang ◽  
S. Lane ◽  
A. Korsak ◽  
J. F. R. Paton ◽  
A. V. Gourine ◽  
...  
Keyword(s):  
Mammalian Brain ◽  
Frontal Brain ◽  
Potential Source ◽  
Neuronal Signalling ◽  
Signalling Molecule ◽  
Principal Source ◽  
Lactate Uptake ◽  
The Brain ◽  
Excitatory Transmitter

Abstract Astrocytes produce and release L-lactate as a potential source of energy for neurons. Here we present evidence that L-lactate, independently of its caloric value, serves as an astrocytic signalling molecule in the locus coeruleus (LC). The LC is the principal source of norepinephrine to the frontal brain and thus one of the most influential modulatory centers of the brain. Optogenetically activated astrocytes release L-lactate, which excites LC neurons and triggers release of norepinephrine. Exogenous L-lactate within the physiologically relevant concentration range mimics these effects. L-lactate effects are concentration-dependent, stereo-selective, independent of L-lactate uptake into neurons and involve a cAMP-mediated step. In vivo injections of L-lactate in the LC evokes arousal similar to the excitatory transmitter, L-glutamate. Our results imply the existence of an unknown receptor for this ‘glio-transmitter’.

scholarly journals Tubulin glycylases and glutamylases have distinct functions in stabilization and motility of ependymal cilia

2013 ◽  
Vol 202 (3) ◽  
pp. 441-451 ◽  
Author(s):  
Montserrat Bosch Grau ◽  
Gloria Gonzalez Curto ◽  
Cecilia Rocha ◽  
Maria M. Magiera ◽  
Patricia Marques Sousa ◽  
...  
Keyword(s):  
Brain Development ◽  
Posttranslational Modifications ◽  
Mammalian Brain ◽  
Potential Importance ◽  
Ependymal Cilia ◽  
Motile Cilia ◽  
Cilia And Flagella ◽  
The Brain

Microtubules are subject to a variety of posttranslational modifications that potentially regulate cytoskeletal functions. Two modifications, glutamylation and glycylation, are highly enriched in the axonemes of most eukaryotes, and might therefore play particularly important roles in cilia and flagella. Here we systematically analyze the dynamics of glutamylation and glycylation in developing mouse ependymal cilia and the expression of the corresponding enzymes in the brain. By systematically screening enzymes of the TTLL family for specific functions in ependymal cilia, we demonstrate that the glycylating enzymes TTLL3 and TTLL8 were required for stability and maintenance of ependymal cilia, whereas the polyglutamylase TTLL6 was necessary for coordinated beating behavior. Our work provides evidence for a functional separation of glutamylating and glycylating enzymes in mammalian ependymal cilia. It further advances the elucidation of the functions of tubulin posttranslational modifications in motile cilia of the mammalian brain and their potential importance in brain development and disease.

scholarly journals The regulatory roles of motile cilia in CSF circulation and hydrocephalus

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Vijay Kumar ◽  
Zobia Umair ◽  
Shiv Kumar ◽  
Ravi Shankar Goutam ◽  
Soochul Park ◽  
...  
Keyword(s):  
Brain Development ◽  
Main Body ◽  
Csf Circulation ◽  
Multiciliated Cells ◽  
Abnormal Accumulation ◽  
Motile Cilia ◽  
The Brain ◽  
Severe Hydrocephalus ◽  
Ependymal Lining

Abstract Background Cerebrospinal fluid (CSF) is an ultra-filtrated colorless brain fluid that circulates within brain spaces like the ventricular cavities, subarachnoid space, and the spine. Its continuous flow serves many primary functions, including nourishment, brain protection, and waste removal. Main body The abnormal accumulation of CSF in brain cavities triggers severe hydrocephalus. Accumulating evidence had indicated that synchronized beats of motile cilia (cilia from multiciliated cells or the ependymal lining in brain ventricles) provide forceful pressure to generate and restrain CSF flow and maintain overall CSF circulation within brain spaces. In humans, the disorders caused by defective primary and/or motile cilia are generally referred to as ciliopathies. The key role of CSF circulation in brain development and its functioning has not been fully elucidated. Conclusions In this review, we briefly discuss the underlying role of motile cilia in CSF circulation and hydrocephalus. We have reviewed cilia and ciliated cells in the brain and the existing evidence for the regulatory role of functional cilia in CSF circulation in the brain. We further discuss the findings obtained for defective cilia and their potential involvement in hydrocephalus. Furthermore, this review will reinforce the idea of motile cilia as master regulators of CSF movements, brain development, and neuronal diseases.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

Microvascular features that suggest effectors of blood-flow regulation in the brain: Evidence by SEM of corrosion casts of intracerebral vessels

1990 ◽  
Vol 48 (3) ◽  
pp. 274-275
Author(s):  
Enrico D.F. Motti ◽  
Hans-Georg Imhof ◽  
Gazi M. Yasargil
Keyword(s):  
Blood Flow ◽  
Perfusion Pressure ◽  
Corrosion Casts ◽  
Cerebral Microcirculation ◽  
Pial Arteries ◽  
Random Occurrence ◽  
Brain Arteries ◽  
Homogeneous Network ◽  
The Brain

Physiologists have devoted most attention in the cerebrovascular tree to the arterial side of the circulation which has been subdivided in three levels: 1) major brain arteries which keep microcirculation constant despite changes in perfusion pressure; 2) pial arteries supposed to be effectors regulating microcirculation; 3) intracerebral arteries supposed to be deprived of active cerebral blood flow regulating devices.The morphological search for microvascular effectors in the cerebrovascular bed has been elusive. The opaque substance of the brain confines in vivo investigation to the superficial pial arteries. Most morphologists had to limit their observation to the random occurrence of a favorable site in the practically two-dimensional thickness of diaphanized histological sections. It is then not surprising most investigators of the cerebral microcirculation refer to an homogeneous network of microvessels interposed between arterioles and venules.We have taken advantage of the excellent depth of focus afforded by the scanning electron microscope (SEM) to investigate corrosion casts obtained injecting a range of experimental animals with a modified Batson's acrylic mixture.

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