scholarly journals Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature

2015 ◽  
Vol 95 (3) ◽  
pp. 953-993 ◽  
Author(s):  
Cenk Ayata ◽  
Martin Lauritzen
Keyword(s):  
Spreading Depression ◽  
Brain Parenchyma ◽  
Cerebral Vasculature ◽  
Transient Wave ◽  
Vascular Elements ◽  
Evolutionarily Conserved ◽  
Central Nervous Systems ◽  
Bidirectional Interactions ◽  
The Impact ◽  
Glial Depolarization

Spreading depression (SD) is a transient wave of near-complete neuronal and glial depolarization associated with massive transmembrane ionic and water shifts. It is evolutionarily conserved in the central nervous systems of a wide variety of species from locust to human. The depolarization spreads slowly at a rate of only millimeters per minute by way of grey matter contiguity, irrespective of functional or vascular divisions, and lasts up to a minute in otherwise normal tissue. As such, SD is a radically different breed of electrophysiological activity compared with everyday neural activity, such as action potentials and synaptic transmission. Seventy years after its discovery by Leão, the mechanisms of SD and its profound metabolic and hemodynamic effects are still debated. What we did learn of consequence, however, is that SD plays a central role in the pathophysiology of a number of diseases including migraine, ischemic stroke, intracranial hemorrhage, and traumatic brain injury. An intriguing overlap among them is that they are all neurovascular disorders. Therefore, the interplay between neurons and vascular elements is critical for our understanding of the impact of this homeostatic breakdown in patients. The challenges of translating experimental data into human pathophysiology notwithstanding, this review provides a detailed account of bidirectional interactions between brain parenchyma and the cerebral vasculature during SD and puts this in the context of neurovascular diseases.

Neuronal and glial activity during spreading depression in cerebral cortex of cat

1975 ◽  
Vol 38 (4) ◽  
pp. 822-841 ◽  
Author(s):  
E. Sugaya ◽  
M. Takato ◽  
Y. Noda
Keyword(s):  
Cerebral Cortex ◽  
Spreading Depression ◽  
Field Potential ◽  
Membrane Depolarization ◽  
Simultaneous Recording ◽  
Neuronal Membrane ◽  
Intracellular Potentials ◽  
Dc Potential ◽  
Glial Membrane ◽  
Glial Depolarization

1. Extra- and intracellular potentials were recorded from neurons and glia during spreading depression (SD) in cerebral cortex of cats. The glial membrane depolarized during SD and the time course of depolarization was concurrent with the surface DC change of SD. The glial depolarization evoked by 20-Hz repetitive cortical stimulation disappeared during the negative DC shift of SD. Simultaneous recording of the extra- and intracellular potentials from a single glial cell with a coaxial microelectrode showed that the extracellular DC potential change was of opposite polarity to the glial intracellular potential, which suggests that the slow glial depolarization concurrent with SD is not the field potential. In contrast to glial cells, the neuronal burst discharges as well as the neuronal membrane depolarization associated with SD did not show a close relationship to SD: the neuronal membrane depolarization and discharge were frequently delayed by 10-3- s from the onset of the SD slow wave. Sometimes SD was observed without accompanying neuronal depolarization. The degree of neuronal depolarization was not always correlated with the amplitude of the negative wave of SD. 2. The effect of tetrodotoxin (TTX) on the negative DC potential of SD was examined. Simultaneous recording of glial membrane potential and the neuronal unit activity as well as extracellular DC potential and surface DC potential during SD was performed and the TTX-treated cortex was compared with the normal state. TTX did not change the DC level of the cerebral cortex. SD could be evoked by KCl when neuronal discharge was completely abolished by TTX application...

Evolutionary origin of the cell nucleus and its functional architecture

2010 ◽  
Vol 48 ◽  
pp. 1-24 ◽  
Author(s):  
Jan Postberg ◽  
Hans J. Lipps ◽  
Thomas Cremer
Keyword(s):  
Cell Nucleus ◽  
Interdisciplinary Research ◽  
Nuclear Organization ◽  
Nuclear Architecture ◽  
Evolutionary Origin ◽  
Cell Type ◽  
Research Strategies ◽  
Evolutionarily Conserved ◽  
Species Specific ◽  
The Impact

Understanding the evolutionary origin of the nucleus and its compartmentalized architecture provides a huge but, as expected, greatly rewarding challenge in the post-genomic era. We start this chapter with a survey of current hypotheses on the evolutionary origin of the cell nucleus. Thereafter, we provide an overview of evolutionarily conserved features of chromatin organization and arrangements, as well as topographical aspects of DNA replication and transcription, followed by a brief introduction of current models of nuclear architecture. In addition to features which may possibly apply to all eukaryotes, the evolutionary plasticity of higher-order nuclear organization is reflected by cell-type- and species-specific features, by the ability of nuclear architecture to adapt to specific environmental demands, as well as by the impact of aberrant nuclear organization on senescence and human disease. We conclude this chapter with a reflection on the necessity of interdisciplinary research strategies to map epigenomes in space and time.

scholarly journals SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes

2021 ◽  
Vol 118 (52) ◽  
pp. e2116668118
Author(s):  
Paulina Pawlica ◽  
Therese A. Yario ◽  
Sylvia White ◽  
Jianhui Wang ◽  
Walter N. Moss ◽  
...  
Keyword(s):  
Small Rna ◽  
Leucine Zipper ◽  
Health Concern ◽  
Interferon Signaling ◽  
Basic Leucine Zipper ◽  
Argonaute Proteins ◽  
Evolutionarily Conserved ◽  
Core Components ◽  
Cellular Machinery ◽  
The Impact

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), continues to be a pressing health concern. In this study, we investigated the impact of SARS-CoV-2 infection on host microRNA (miRNA) populations in three human lung-derived cell lines, as well as in nasopharyngeal swabs from SARS-CoV-2–infected individuals. We did not detect any major and consistent differences in host miRNA levels after SARS-CoV-2 infection. However, we unexpectedly discovered a viral miRNA-like small RNA, named CoV2-miR-O7a (for SARS-CoV-2 miRNA-like ORF7a-derived small RNA). Its abundance ranges from low to moderate as compared to host miRNAs and it associates with Argonaute proteins—core components of the RNA interference pathway. We identify putative targets for CoV2-miR-O7a, including Basic Leucine Zipper ATF-Like Transcription Factor 2 (BATF2), which participates in interferon signaling. We demonstrate that CoV2-miR-O7a production relies on cellular machinery, yet is independent of Drosha protein, and is enhanced by the presence of a strong and evolutionarily conserved hairpin formed within the ORF7a sequence.

scholarly journals Microglia motility depends on neuronal activity and promotes structural plasticity in the hippocampus

2019 ◽  
Author(s):  
Felix C. Nebeling ◽  
Stefanie Poll ◽  
Lena C. Schmid ◽  
Manuel Mittag ◽  
Julia Steffen ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Dendritic Spines ◽  
Synapse Formation ◽  
Brain Parenchyma ◽  
Two Photon ◽  
Contact Rates ◽  
Health And Disease ◽  
The Impact ◽  
The Brain

AbstractMicroglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.

Cranioplasty Reverses Dysfunction of the Solutes Distribution in the Brain Parenchyma After Decompressive Craniectomy

Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 1064-1069 ◽  
Author(s):  
Alin Borha ◽  
Audrey Chagnot ◽  
Romain Goulay ◽  
Evelyne Emery ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Decompressive Craniectomy ◽  
Early Time ◽  
Brain Parenchyma ◽  
Late Time ◽  
Perivascular Spaces ◽  
Early Time Point ◽  
The Impact ◽  
The Brain ◽  
Brain Homeostasis ◽  
Time Point

Abstract Background Solutes distribution by the intracranial cerebrospinal fluid (CSF) fluxes along perivascular spaces and through interstitial fluid (ISF) play a key role in the clearance of brain metabolites, with essential functions in maintaining brain homeostasis. Objective To investigate the impact of decompressive craniectomy (DC) and cranioplasty (CP) on the efficacy of solutes distribution by the intracranial CSF and ISF flux. Methods Mice were allocated in 3 groups: sham surgery, DC, and DC followed by CP. The solutes distribution in the brain parenchyma was assessed using T1 magnetic resonance imaging after injection of DOTA-Gadolinium in the cisterna magna. This evaluation was performed at an early time point following DC (after 2 d) and at a later time point (after 15 d). We evaluated the solutes distribution in the whole brain and in the region underneath the DC area. Results Our results demonstrate that the global solutes distribution in the brain parenchyma is impaired after DC in mice, both at early and late time-points. However, there was no impact of DC on the solutes distribution just under the craniectomy. We then provide evidence that this impairment was reversed by CP. Conclusion The solute distribution in the brain parenchyma by the CSF and ISF is impaired by DC, a phenomenon reversed by CP.

scholarly journals Mechanism of Coup and Contrecoup Injuries Induced by a Knock-Out Punch

2020 ◽  
Vol 25 (2) ◽  
pp. 22 ◽  
Author(s):  
Milan Toma ◽  
Rosalyn Chan-Akeley ◽  
Christopher Lipari ◽  
Sheng-Han Kuo
Keyword(s):  
Cerebrospinal Fluid ◽  
Interaction Model ◽  
Brain Parenchyma ◽  
Primary Objective ◽  
Element Analysis ◽  
Knock Out ◽  
Particle Hydrodynamics ◽  
Smoothed Particle ◽  
The Impact ◽  
The Brain

Primary Objective: The interaction of cerebrospinal fluid with the brain parenchyma in an impact scenario is studied. Research Design: A computational fluid-structure interaction model is used to simulate the interaction of cerebrospinal fluid with a comprehensive brain model. Methods and Procedures: The method of smoothed particle hydrodynamics is used to simulate the fluid flow, induced by the impact, simultaneously with finite element analysis to solve the large deformations in the brain model. Main Outcomes and Results: Mechanism of injury resulting in concussion is demonstrated. The locations with the highest stress values on the brain parenchyma are shown. Conclusions: Our simulations found that the damage to the brain resulting from the contrecoup injury is more severe than that resulting from the coup injury. Additionally, we show that the contrecoup injury does not always appear on the side opposite from where impact occurs.

scholarly journals Long Term Pharmacological Perturbation of Autophagy in Mice: Are HCQ Injections a Relevant Choice?

Biomedicines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 47 ◽  
Author(s):  
Jean-Daniel Masson ◽  
Benoit Blanchet ◽  
Baptiste Periou ◽  
François-Jérôme Authier ◽  
Baharia Mograbi ◽  
...  
Keyword(s):  
Mouse Models ◽  
In Vivo Studies ◽  
Loss Of Function ◽  
Evolutionarily Conserved ◽  
Atg Genes ◽  
Conditional Inhibition ◽  
The Impact ◽  
Catabolic Process

Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved catabolic process whose loss-of-function has been linked to a growing list of pathologies. Knockout mouse models of key autophagy genes have been instrumental in the demonstration of the critical functions of autophagy, but they display early lethality, neurotoxicity and unwanted autophagy-independent phenotypes, limiting their applications for in vivo studies. To avoid problems encountered with autophagy-null transgenic mice, we investigated the possibility of disturbing autophagy pharmacologically in the long term. Hydroxychloroquine (HCQ) ip injections were done in juvenile and adult C57bl/6j mice, at range doses adapted from the human malaria prophylactic treatment. The impact on autophagy was assessed by western-blotting, and juvenile neurodevelopment and adult behaviours were evaluated for four months. Quite surprisingly, our results showed that HCQ treatment in conditions used in this study neither impacted autophagy in the long term in several tissues and organs nor altered neurodevelopment, adult behaviour and motor capabilities. Therefore, we recommend for future long-term in vivo studies of autophagy, to use genetic mouse models allowing conditional inhibition of selected Atg genes in appropriate lineage cells instead of HCQ treatment, until it could be successfully revisited using higher HCQ doses and/or frequencies with acceptable toxicity.

scholarly journals Mechanisms of spreading depolarization in vertebrate and insect central nervous systems

2016 ◽  
Vol 116 (3) ◽  
pp. 1117-1127 ◽  
Author(s):  
Kristin E. Spong ◽  
R. David Andrew ◽  
R. Meldrum Robertson
Keyword(s):  
Locusta Migratoria ◽  
Model Systems ◽  
Control Mechanisms ◽  
Cellular Mechanisms ◽  
Nervous Systems ◽  
Spreading Depolarization ◽  
Metathoracic Ganglion ◽  
Evolutionarily Conserved ◽  
Central Nervous Systems ◽  
The Central Nervous System

Spreading depolarization (SD) is generated in the central nervous systems of both vertebrates and invertebrates. SD manifests as a propagating wave of electrical depression caused by a massive redistribution of ions. Mammalian SD underlies a continuum of human pathologies from migraine to stroke damage, whereas insect SD is associated with environmental stress-induced neural shutdown. The general cellular mechanisms underlying SD seem to be evolutionarily conserved throughout the animal kingdom. In particular, SD in the central nervous system of Locusta migratoria and Drosophila melanogaster has all the hallmarks of mammalian SD. Locust SD is easily induced and monitored within the metathoracic ganglion (MTG) and can be modulated both pharmacologically and by preconditioning treatments. The finding that the fly brain supports repetitive waves of SD is relatively recent but noteworthy, since it provides a genetically tractable model system. Due to the human suffering caused by SD manifestations, elucidating control mechanisms that could ultimately attenuate brain susceptibility is essential. Here we review mechanisms of SD focusing on the similarities between mammalian and insect systems. Additionally we discuss advantages of using invertebrate model systems and propose insect SD as a valuable model for providing new insights to mammalian SD.

scholarly journals NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy

2020 ◽  
Author(s):  
Nina McTiernan ◽  
◽  
Harinder Gill ◽  
Carlos E. Prada ◽  
Harry Pachajoa ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Genetic Disorders ◽  
Cellular Functions ◽  
Functional Studies ◽  
Phenotypic Spectrum ◽  
Independent Functions ◽  
Evolutionarily Conserved ◽  
Human Proteins ◽  
The Impact

Abstract Nearly half of all human proteins are acetylated at their N-termini by the NatA N-terminal acetyltransferase complex. NAA10 is evolutionarily conserved as the catalytic subunit of NatA in complex with NAA15, but may also have NatA-independent functions. Several NAA10 variants are associated with genetic disorders. The phenotypic spectrum includes developmental delay, intellectual disability, and cardiac abnormalities. Here, we have identified the previously undescribed NAA10 c.303C>A and c.303C>G p.(N101K) variants in two unrelated girls. These girls have developmental delay, but they both also display hemihypertrophy a feature normally not observed or registered among these cases. Functional studies revealed that NAA10 p.(N101K) is completely impaired in its ability to bind NAA15 and to form an enzymatically active NatA complex. In contrast, the integrity of NAA10 p.(N101K) as a monomeric acetyltransferase is intact. Thus, this NAA10 variant may represent the best example of the impact of NatA mediated N-terminal acetylation, isolated from other potential NAA10-mediated cellular functions and may provide important insights into the phenotypes observed in individuals expressing pathogenic NAA10 variants.

scholarly journals Astrocytic Modulation of Neuronal Activity in the Suprachiasmatic Nucleus: Insights from Mathematical Modeling

2020 ◽  
Vol 35 (3) ◽  
pp. 287-301
Author(s):  
Natthapong Sueviriyapan ◽  
Chak Foon Tso ◽  
Erik D. Herzog ◽  
Michael A. Henson
Keyword(s):  
Circadian Rhythm ◽  
Suprachiasmatic Nucleus ◽  
Neuronal Activity ◽  
Clock Genes ◽  
Rhythmic Activity ◽  
Neuronal Population ◽  
Circadian Period ◽  
Circadian Oscillators ◽  
Bidirectional Interactions ◽  
The Impact

The suprachiasmatic nucleus (SCN) of the hypothalamus consists of a highly heterogeneous neuronal population networked together to allow precise and robust circadian timekeeping in mammals. While the critical importance of SCN neurons in regulating circadian rhythms has been extensively studied, the roles of SCN astrocytes in circadian system function are not well understood. Recent experiments have demonstrated that SCN astrocytes are circadian oscillators with the same functional clock genes as SCN neurons. Astrocytes generate rhythmic outputs that are thought to modulate neuronal activity through pre- and postsynaptic interactions. In this study, we developed an in silico multicellular model of the SCN clock to investigate the impact of astrocytes in modulating neuronal activity and affecting key clock properties such as circadian rhythmicity, period, and synchronization. The model predicted that astrocytes could alter the rhythmic activity of neurons via bidirectional interactions at tripartite synapses. Specifically, astrocyte-regulated extracellular glutamate was predicted to increase neuropeptide signaling from neurons. Consistent with experimental results, we found that astrocytes could increase the circadian period and enhance neural synchronization according to their endogenous circadian period. The impact of astrocytic modulation of circadian rhythm amplitude, period, and synchronization was predicted to be strongest when astrocytes had periods between 0 and 2 h longer than neurons. Increasing the number of neurons coupled to the astrocyte also increased its impact on period modulation and synchrony. These computational results suggest that signals that modulate astrocytic rhythms or signaling (e.g., as a function of season, age, or treatment) could cause disruptions in circadian rhythm or serve as putative therapeutic targets.

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