scholarly journals Extracellular Tau and Glymphatic Influx in Sleep and Anesthesia

2019 ◽  
Author(s):  
J. Shashi Kiran Reddy
Keyword(s):  
Sleep Deprivation ◽  
Protein Level ◽  
Interstitial Fluid ◽  
Synaptic Strength ◽  
Synaptic Activity ◽  
Major Portion ◽  
Neuronal Metabolism ◽  
Potential Factors ◽  
The Brain

Holth and colleagues recently examined how the sleep-wake cycle influence/regulate the amount of metabolic waste, mainly extracellular tau, in the brain (1). They report that interstitial fluid (ISF) tau in mice increases approximately by 90% during normal wakefulness versus sleep, and 100% during sleep deprivation (SD) as compared to 50% increase in CSF tau in humans. During SD, humans also registered increased levels of certain proteins like tau and synuclein with no significant changes in the levels of other neural proteins, suggesting some specificity in sleep/protein level interaction. This indicates that the above changes may be due to increased release of certain proteins rather than changes in global ISF clearance, which authors attribute to elevated neuronal metabolism/synaptic strength during SD and wakefulness (2). A major portion of the extracellular tau in the brain results from high neuronal/synaptic activity (2,3), but, we suggest, other potential factors may also add up to elevate the levels of tau normally present in ISF.

Fisiopatología de la hidrocefália idiopática de presión normal (parte 3): sistemaa glinfático

2016 ◽  
Vol 21 (2) ◽  
pp. 28-37
Author(s):  
Oscar Solís-Salgado ◽  
José Luis López-Payares ◽  
Mauricio Ayala-González
Keyword(s):  
Amyloid Beta ◽  
Interstitial Fluid ◽  
Amyloid Β ◽  
Bulk Flow ◽  
Polyethylene Glycols ◽  
Brain Interstitial Fluid ◽  
El Sistema ◽  
Arterial Pulsation ◽  
The Brain

Las vías de drenaje solutos del sistema nervioso central (SNC) participan en el recambio de liquido intersticial con el líquido cefalorraquídeo (LIT-LCR), generando un estado de homeostasis. Las alteraciones dentro de este sistema homeostático afectará la eliminación de solutos del espacio intersticial (EIT) como el péptido βa y proteína tau, los cuales son sustancias neurotóxicas para el SNC. Se han utilizado técnicas experimentales para poder analizar el intercambio LIT-LCR, las cuales revelan que este intercambio tiene una estructura bien organizada. La eliminación de solutos del SNC no tiene una estructura anatómica propiamente, se han descubierto vías de eliminación de solutos a través de marcadores florecentes en el espacio subaracnoideo, cisternas de la base y sistema ventricular que nos permiten observar una serie de vías ampliamente distribuidas en el cerebro. El LCR muestra que tiene una función linfática debido a su recambio con el LIT a lo largo de rutas paravasculares. Estos espacios que rodean la superficie arterial así como los espacios de Virchow-Robin y el pie astrocitico junto con la AQP-4, facilitan la entrada de LCR para-arterial y el aclaramiento de LIT para-venoso dentro del cerebro. El flujo y dirección que toma el LCR por estas estructuras, es conducido por la pulsación arterial. Esta función será la que finalmente llevara a la eliminación de estas sustancias neurotóxicas. En base a la dependencia de este flujo para la eliminación de sustancias se propone que el sistema sea llamado “ la Vía Glinfática”. La bibliografía así como las limitaciones que se encuentran en esta revisión están dadas por la metodología de búsqueda que ha sido realizada principalmente en PubMed utilizando los siguientes términos Mesh: Cerebral Arterial Pulsation, the brain via paravascular, drainage of amyloid-beta, bulk flow of brain interstitial fluid, radiolabeled polyethylene glycols and albumin, amyloid-β, the perivascular astroglial sheath, Brain Glymphatic Transport.

scholarly journals Time to Be SHY? Some Comments on Sleep and Synaptic Homeostasis

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Giulio Tononi ◽  
Chiara Cirelli
Keyword(s):  
Synaptic Strength ◽  
Universal Function ◽  
Systematic Bias ◽  
Synaptic Homeostasis ◽  
The Face ◽  
Essential Function ◽  
Function Of Sleep ◽  
The Brain

Sleep must serve an essential, universal function, one that offsets the risk of being disconnected from the environment. The synaptic homeostasis hypothesis (SHY) is an attempt to identify this essential function. Its core claim is that sleep is needed to reestablish synaptic homeostasis, which is challenged by the remarkable plasticity of the brain. In other words, sleep is “the price we pay for plasticity.” In this issue, M. G. Frank reviewed several aspects of the hypothesis and raised several issues. The comments below provide a brief summary of the motivations underlying SHY and clarify that SHY is a hypothesis not about specific mechanisms, but about a universal, essential function of sleep. This function is the preservation of synaptic homeostasis in the face of a systematic bias toward a net increase in synaptic strength—a challenge that is posed by learning during adult wake, and by massive synaptogenesis during development.

scholarly journals Bystander Attenuation of Neuronal and Astrocyte Intercellular Communication by Murine Cytomegalovirus Infection of Glia

2007 ◽  
Vol 81 (13) ◽  
pp. 7286-7292 ◽  
Author(s):  
Winson S. C. Ho ◽  
Anthony N. van den Pol
Keyword(s):  
Intercellular Communication ◽  
Neuronal Development ◽  
Primary Cultures ◽  
Synaptic Activity ◽  
Murine Cytomegalovirus ◽  
Intercellular Signaling ◽  
Mcmv Infection ◽  
High Potassium ◽  
Infected Cells ◽  
The Brain

ABSTRACT Astrocytes are the first cells infected by murine cytomegalovirus (MCMV) in primary cultures of brain. These cells play key roles in intercellular signaling and neuronal development, and they modulate synaptic activity within the nervous system. Using ratiometric fura-2 digital calcium imaging of >8,000 neurons and glia, we found that MCMV-infected astrocytes showed an increase in intracellular basal calcium levels and an enhanced response to neuroactive substances, including glutamate and ATP, and to high potassium levels. Cultured neurons with no sign of MCMV infection showed attenuated synaptic signaling after infection of the underlying astrocyte substrate, and intercellular communication between astrocytes with no sign of infection was reduced by the presence of infected glia. These bystander effects would tend to cause further deterioration of cellular communication in the brain in addition to the problems caused by the loss of directly infected cells.

Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain

2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker
Keyword(s):  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Neurotrophin 3 ◽  
New Findings ◽  
The Central Nervous System ◽  
The Brain

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.

scholarly journals Partial loss of CFIm25 causes learning deficits and aberrant neuronal alternative polyadenylation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Callison E Alcott ◽  
Hari Krishna Yalamanchili ◽  
Ping Ji ◽  
Meike E van der Heijden ◽  
Alexander Saltzman ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Protein Level ◽  
Alternative Polyadenylation ◽  
Copy Number Variations ◽  
Human Stem Cell ◽  
Partial Loss ◽  
Learning Deficits ◽  
Cortical Hyperexcitability ◽  
The Brain ◽  
Cognate Protein

We previously showed that NUDT21-spanning copy-number variations (CNVs) are associated with intellectual disability (Gennarino et al., 2015). However, the patients’ CNVs also included other genes. To determine if reduced NUDT21 function alone can cause disease, we generated Nudt21+/- mice to mimic NUDT21-deletion patients. We found that although these mice have 50% reduced Nudt21 mRNA, they only have 30% less of its cognate protein, CFIm25. Despite this partial protein-level compensation, the Nudt21+/- mice have learning deficits, cortical hyperexcitability, and misregulated alternative polyadenylation (APA) in their hippocampi. Further, to determine the mediators driving neural dysfunction in humans, we partially inhibited NUDT21 in human stem cell-derived neurons to reduce CFIm25 by 30%. This induced APA and protein level misregulation in hundreds of genes, a number of which cause intellectual disability when mutated. Altogether, these results show that disruption of NUDT21-regulated APA events in the brain can cause intellectual disability.

scholarly journals Research on the Glial–Lymphatic System and Its Relationship With Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Danhua Ding ◽  
Xinyu Wang ◽  
Qianqian Li ◽  
Lanjun Li ◽  
Jun Wu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Severity ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Pathological Change ◽  
Vital Role ◽  
Aquaporin 4 ◽  
Β Amyloid ◽  
The Brain

Metabolic waste clearance is essential to maintain body homeostasis, in which the lymphatic system plays a vital role. Conversely, in recent years, studies have identified the glial–lymphatic system in the brain, which primarily comprises the inflow of fluid along the para-arterial space. Aquaporin-4 mediates the convection of interstitial fluid in the brain and outflow along the paravenous space. β-Amyloid deposition is a characteristic pathological change in Alzheimer’s disease, and some studies have found that the glial–lymphatic system plays an important role in its clearance. Thus, the glial–lymphatic system may influence Alzheimer’s disease severity and outcome; therefore, this review summarizes the current and available research on the glial–lymphatic system and Alzheimer’s disease.

scholarly journals Simultaneous EEG and fMRI: towards the characterization of structure and dynamics of brain networks

2013 ◽  
Vol 15 (3) ◽  
pp. 381-386 ◽  
Keyword(s):  
Spatial Resolution ◽  
Brain Function ◽  
Methodological Approach ◽  
Brain Networks ◽  
Indirect Measurement ◽  
Synaptic Activity ◽  
High Temporal Resolution ◽  
Neural Mass ◽  
The Brain

Progress in the understanding of normal and disturbed brain function is critically dependent on the methodological approach that is applied. Both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are extremely efficient methods for the assessment of human brain function. The specific appeal of the combination is related to the fact that both methods are complementary in terms of basic aspects: EEG is a direct measurement of neural mass activity and provides high temporal resolution. FMRI is an indirect measurement of neural activity and based on hemodynamic changes, and offers high spatial resolution. Both methods are very sensitive to changes of synaptic activity, suggesting that with simultaneous EEG and fMRI the same neural events can be characterized with both high temporal and spatial resolution. Since neural oscillations that can be assessed with EEG are a key mechanism for multi-site communication in the brain, EEG-fMRI can offer new insights into the connectivity mechanisms of brain networks.

scholarly journals Fragile X syndrome patient-derived neurons developing in the mouse brain show FMR1 -dependent phenotypes

2021 ◽  
Author(s):  
Marine A Krzisch ◽  
Hao A Wu ◽  
Bingbing Yuan ◽  
Troy W. Whitfield ◽  
X. Shawn Liu ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Neuronal Development ◽  
Fragile X ◽  
In Vitro Models ◽  
Synaptic Activity ◽  
Human Neurons ◽  
Induced Pluripotent ◽  
And Function ◽  
The Brain

Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The transplanted cells populated the brain and a proportion differentiated into neurons and glial cells. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons after an initial delay. Additionally, increased percentages of Arc- and Egr1-positive FXS neurons and wider dendritic protrusions of mature FXS striatal medium spiny neurons pointed to an increase in synaptic activity and synaptic strength as compared to control. This transplantation approach provides new insights into the alterations of neuronal development in FXS by facilitating physiological development of cells in a 3D context, and could be used to test new therapeutic compounds correcting neuronal development defects in FXS.

scholarly journals Supportive or information-processing functions of the mature protoplasmic astrocyte in the mammalian CNS? A critical appraisal

2007 ◽  
Vol 3 (3) ◽  
pp. 181-189 ◽  
Author(s):  
Harold K. Kimelberg
Keyword(s):  
Information Processing ◽  
Blood Vessel ◽  
Critical Appraisal ◽  
Vessel Diameter ◽  
Synaptic Activity ◽  
Metabolic Substrates ◽  
Processing Properties ◽  
New Evidence ◽  
The Brain ◽  
Domain Concept

AbstractIt has been proposed that astrocytes should no longer be viewed purely as support cells for neurons, such as providing a constant environment and metabolic substrates, but that they should also be viewed as being involved in affecting synaptic activity in an active way and, therefore, an integral part of the information-processing properties of the brain. This essay discusses the possible differences between a support and an instructive role, and concludes that any distinction has to be blurred. In view of this, and a brief overview of the nature of the data, the new evidence seems insufficient to conclude that the physiological roles of mature astrocytes go beyond a general support role. I propose a model of mature protoplasmic astrocyte function that is drawn from the most recent data on their structure, the domain concept and their syncytial characteristics, of an independent rather than integrative functioning of the ends of each process where the activities that affect synaptic activity and blood vessel diameter will be concentrated.

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