Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain

Over the past 20 years, analyses of single brain cell genomes have revealed that the brain is composed of cells with myriad distinct genomes: the brain is a genomic mosaic, generated by a host of DNA sequence-altering processes that occur somatically and do not affect the germline. As such, these sequence changes are not heritable. Some processes appear to occur during neurogenesis, when cells are mitotic, whereas others may also function in post-mitotic cells. Here, we review multiple forms of DNA sequence alterations that have now been documented: aneuploidies and aneusomies, smaller copy number variations (CNVs), somatic repeat expansions, retrotransposons, genomic cDNAs (gencDNAs) associated with somatic gene recombination (SGR), and single nucleotide variations (SNVs). A catch-all term of DNA content variation (DCV) has also been used to describe the overall phenomenon, which can include multiple forms within a single cell’s genome. A requisite step in the analyses of genomic mosaicism is ongoing technology development, which is also discussed. Genomic mosaicism alters one of the most stable biological molecules, DNA, which may have many repercussions, ranging from normal functions including effects of aging, to creating dysfunction that occurs in neurodegenerative and other brain diseases, most of which show sporadic presentation, unlinked to causal, heritable genes.

Download Full-text

Biological response of the organism to the introduction of metal nanocomposites

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2019-59-9-761-762 ◽

2020 ◽

pp. 761-762

Author(s):

L. M. Sosedova ◽

V. S. Rukavishnikov ◽

E. A. Titov

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Biological Response ◽

Brain Cell ◽

Metal Nanocomposites ◽

The Brain

The results of a study on rats toxicity of nanoparticles of metals bismuth, gadolinium and silver encapsulated in a natural biopolymer matrix arabinogalactan are presented. When intake of nanocomposite of silver revealed the readiness of the brain cell to apoptosis. The effect of bismuth and gadolinium nanocomposites did not cause an increase in the process of programmed cell death.

Download Full-text

A new method to predict anomaly in brain network based on graph deep learning

Reviews in the Neurosciences ◽

10.1515/revneuro-2019-0108 ◽

2020 ◽

Vol 31 (6) ◽

pp. 681-689

Author(s):

Jalal Mirakhorli ◽

Hamidreza Amindavar ◽

Mojgan Mirakhorli

Keyword(s):

Deep Learning ◽

Large Scale ◽

Brain Plasticity ◽

Brain Network ◽

High Order ◽

Brain Diseases ◽

Simultaneous Occurrence ◽

Generative Adversarial Network ◽

The Brain ◽

Brain Connections

AbstractFunctional magnetic resonance imaging a neuroimaging technique which is used in brain disorders and dysfunction studies, has been improved in recent years by mapping the topology of the brain connections, named connectopic mapping. Based on the fact that healthy and unhealthy brain regions and functions differ slightly, studying the complex topology of the functional and structural networks in the human brain is too complicated considering the growth of evaluation measures. One of the applications of irregular graph deep learning is to analyze the human cognitive functions related to the gene expression and related distributed spatial patterns. Since a variety of brain solutions can be dynamically held in the neuronal networks of the brain with different activity patterns and functional connectivity, both node-centric and graph-centric tasks are involved in this application. In this study, we used an individual generative model and high order graph analysis for the region of interest recognition areas of the brain with abnormal connection during performing certain tasks and resting-state or decompose irregular observations. Accordingly, a high order framework of Variational Graph Autoencoder with a Gaussian distributer was proposed in the paper to analyze the functional data in brain imaging studies in which Generative Adversarial Network is employed for optimizing the latent space in the process of learning strong non-rigid graphs among large scale data. Furthermore, the possible modes of correlations were distinguished in abnormal brain connections. Our goal was to find the degree of correlation between the affected regions and their simultaneous occurrence over time. We can take advantage of this to diagnose brain diseases or show the ability of the nervous system to modify brain topology at all angles and brain plasticity according to input stimuli. In this study, we particularly focused on Alzheimer’s disease.

Download Full-text

Effect of Water and Ethanol Extracts from Hericium erinaceus Solid-State Fermented Wheat Product on the Protection and Repair of Brain Cells in Zebrafish Embryos

Molecules ◽

10.3390/molecules26113297 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3297

Author(s):

Shun-Kuo Sun ◽

Chun-Yi Ho ◽

Wei-Yang Yen ◽

Su-Der Chen

Keyword(s):

Solid State ◽

Brain Cell ◽

Hot Water ◽

Raw Material ◽

Brain Cells ◽

Zebrafish Embryos ◽

Hericium Erinaceus ◽

Water Extracts ◽

The Brain ◽

Wheat Product

Extracts from Hericium erinaceus can cause neural cells to produce nerve growth factor (NGF) and protect against neuron death. The objective of this study was to evaluate the effects of ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product on the brain cells of zebrafish embryos in both pre-dosing protection mode and post-dosing repair mode. The results showed that 1% ethanol could effectively promote zebrafish embryo brain cell death. Both 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product protected brain cells and significantly reduced the death of brain cells caused by 1% ethanol treatment in zebrafish. Moreover, the zebrafish embryos were immersed in 1% ethanol for 4 h to cause brain cell damage and were then transferred and soaked in the 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product to restore the brain cells damaged by the 1% ethanol. However, the 200 ppm extracts from the unfermented wheat medium had no protective and repairing effects. Moreover, 200 ppm of ethanol and water extracts from H. erinaceus fruiting body had less significant protective and restorative effects on the brain cells of zebrafish embryos. Both the ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product could protect and repair the brain cells of zebrafish embryos damaged by 1% ethanol. Therefore, it has great potential as a raw material for neuroprotective health product.

Download Full-text

The brain timewise: how timing shapes and supports brain function

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2014.0170 ◽

2015 ◽

Vol 370 (1668) ◽

pp. 20140170 ◽

Cited By ~ 39

Author(s):

Riitta Hari ◽

Lauri Parkkonen

Keyword(s):

Human Brain ◽

Brain Imaging ◽

Brain Function ◽

Temporal Dynamics ◽

Generative Models ◽

Network Activity ◽

Brain Diseases ◽

Specific Information ◽

Non Invasive ◽

The Brain

We discuss the importance of timing in brain function: how temporal dynamics of the world has left its traces in the brain during evolution and how we can monitor the dynamics of the human brain with non-invasive measurements. Accurate timing is important for the interplay of neurons, neuronal circuitries, brain areas and human individuals. In the human brain, multiple temporal integration windows are hierarchically organized, with temporal scales ranging from microseconds to tens and hundreds of milliseconds for perceptual, motor and cognitive functions, and up to minutes, hours and even months for hormonal and mood changes. Accurate timing is impaired in several brain diseases. From the current repertoire of non-invasive brain imaging methods, only magnetoencephalography (MEG) and scalp electroencephalography (EEG) provide millisecond time-resolution; our focus in this paper is on MEG. Since the introduction of high-density whole-scalp MEG/EEG coverage in the 1990s, the instrumentation has not changed drastically; yet, novel data analyses are advancing the field rapidly by shifting the focus from the mere pinpointing of activity hotspots to seeking stimulus- or task-specific information and to characterizing functional networks. During the next decades, we can expect increased spatial resolution and accuracy of the time-resolved brain imaging and better understanding of brain function, especially its temporal constraints, with the development of novel instrumentation and finer-grained, physiologically inspired generative models of local and network activity. Merging both spatial and temporal information with increasing accuracy and carrying out recordings in naturalistic conditions, including social interaction, will bring much new information about human brain function.

Download Full-text

Transient Receptor Potential Vanilloid in the Brain Gliovascular Unit: Prospective Targets in Therapy

Pharmaceutics ◽

10.3390/pharmaceutics13030334 ◽

2021 ◽

Vol 13 (3) ◽

pp. 334

Author(s):

Huilong Luo ◽

Xavier Declèves ◽

Salvatore Cisternino

Keyword(s):

Transient Receptor Potential ◽

Receptor Potential ◽

Brain Diseases ◽

Transient Receptor Potential Vanilloid ◽

Main Role ◽

Trpv Channels ◽

Gliovascular Unit ◽

Transient Receptor ◽

The Brain

The gliovascular unit (GVU) is composed of the brain microvascular endothelial cells forming blood–brain barrier and the neighboring surrounding “mural” cells (e.g., pericytes) and astrocytes. Modulation of the GVU/BBB features could be observed in a variety of vascular, immunologic, neuro-psychiatric diseases, and cancers, which can disrupt the brain homeostasis. Ca2+ dynamics have been regarded as a major factor in determining BBB/GVU properties, and previous studies have demonstrated the role of transient receptor potential vanilloid (TRPV) channels in modulating Ca2+ and BBB/GVU properties. The physiological role of thermosensitive TRPV channels in the BBB/GVU, as well as their possible therapeutic potential as targets in treating brain diseases via preserving the BBB are reviewed. TRPV2 and TRPV4 are the most abundant isoforms in the human BBB, and TRPV2 was evidenced to play a main role in regulating human BBB integrity. Interspecies differences in TRPV2 and TRPV4 BBB expression complicate further preclinical validation. More studies are still needed to better establish the physiopathological TRPV roles such as in astrocytes, vascular smooth muscle cells, and pericytes. The effect of the chronic TRPV modulation should also deserve further studies to evaluate their benefit and innocuity in vivo.

Download Full-text

Exploration of beneficial and deleterious effects of inflammation in stroke: dynamics of inflammation cells

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2009.0184 ◽

2009 ◽

Vol 367 (1908) ◽

pp. 4699-4716 ◽

Cited By ~ 15

Author(s):

Taïssia Lelekov-Boissard ◽

Guillemette Chapuisat ◽

Jean-Pierre Boissel ◽

Emmanuel Grenier ◽

Marie-Aimée Dronne

Keyword(s):

Immune Cells ◽

Blood Cells ◽

Inflammatory Process ◽

Living Cells ◽

Therapeutic Strategies ◽

Brain Parenchyma ◽

Brain Cell ◽

Cytokines And Chemokines ◽

The Brain

The inflammatory process during stroke consists of activation of resident brain microglia and recruitment of leucocytes, namely neutrophils and monocytes/macrophages. During inflammation, microglial cells, neutrophils and macrophages secrete inflammatory cytokines and chemokines, and phagocytize dead cells. The recruitment of blood cells (neutrophils and macrophages) is mediated by the leucocyte–endothelium interactions and more specifically by cell adhesion molecules. A mathematical model is proposed to represent the dynamics of various brain cells and of immune cells (neutrophils and macrophages). This model is based on a set of six ordinary differential equations and explores the beneficial and deleterious effects of inflammation, respectively phagocytosis by immune cells and the release of pro-inflammatory mediators and nitric oxide (NO). The results of our simulations are qualitatively consistent with those observed in experiments in vivo and would suggest that the increase of phagocytosis could contribute to the increase of the percentage of living cells. The inhibition of the production of cytokines and NO and the blocking of neutrophil and macrophage infiltration into the brain parenchyma led also to the improvement of brain cell survival. This approach may help to explore the respective contributions of the beneficial and deleterious roles of the inflammatory process in stroke, and to study various therapeutic strategies in order to reduce stroke damage.

Download Full-text

Enkephalin, Drug Addiction and Acupuncture

The American Journal of Chinese Medicine ◽

10.1142/s0192415x77000038 ◽

1977 ◽

Vol 05 (01) ◽

pp. 25-30 ◽

Cited By ~ 8

Author(s):

Gregory S. Chen

Keyword(s):

Nervous System ◽

Opiate Receptors ◽

Basic Research ◽

Brain Cell ◽

Withdrawal Symptoms ◽

Opiate Withdrawal ◽

Acupuncture Analgesia ◽

Acupuncture Stimulation ◽

Natural Ligand ◽

The Brain

From the results of clinical and basic research, there is clear evidence the acupuncture analgesia is closely associated with the nervous system, especially the central nervous system. Stimulation of certain acupuncture loci which have been used for analgesia during operations aslo can calm the withdrawal symptoms of morphine and heroin addicts. Acupuncture analgesia can be antagonized by the specific narcotic antagonist, naloxone. These findings suggest the factor or factors produced by acupuncture stimulation would also have agonist activity on opiate receptors. Moreover, the morphine receptors are most concentrated in those parts of the brain concerned with preception of pain and the pathway of acupuncture stimulation. Since the opiate receptors are associated with the synaptic fraction of brain cell membrane preparations, the natural ligand of these receptors may be a neuro-transmitter. Enkephalin has stronger binding affinity to opiate receptors than morphine, which suggests that it is the natural ligand for these receptors. In other words, enkephalin might be the natural "pain killer" produced in the brain to suppress pain. If we summate all the information available now, it is possible to suggest that enkephalin may be the product of the nervous system released by acupuncture stimulation to create an analgesic effect as well as suppress opiate withdrawal symptoms.

Download Full-text

PHENOMENOLOGICAL ARCHITECTURE OF A MIND AND OPERATIONAL ARCHITECTONICS OF THE BRAIN: THE UNIFIED METASTABLE CONTINUUM

New Mathematics and Natural Computation ◽

10.1142/s1793005709001258 ◽

2009 ◽

Vol 05 (01) ◽

pp. 221-244 ◽

Cited By ~ 31

Author(s):

ANDREW A. FINGELKURTS ◽

ALEXANDER A. FINGELKURTS ◽

CARLOS F. H. NEVES

Keyword(s):

Distributed Computing ◽

Brain Activity ◽

Brain Diseases ◽

Machine Consciousness ◽

Self Organized ◽

Conscious Level ◽

The Brain ◽

Activity Organization

In our contribution we will observe phenomenal architecture of a mind and operational architectonics of the brain and will show their intimate connectedness within a single integrated metastable continuum. The notion of operation of different complexity is the fundamental and central one in bridging the gap between brain and mind: it is precisely by means of this notion that it is possible to identify what at the same time belongs to the phenomenal conscious level and to the neurophysiological level of brain activity organization, and what mediates between them. Implications for linguistic semantics, self-organized distributed computing algorithms, artificial machine consciousness, and diagnosis of dynamic brain diseases will be discussed briefly.

Download Full-text