Activation of the Brain to Postpone Dementia: A Concept Originating from Postmortem Human Brain Studies

Almost 150 papers about brain lymphatics have been published in the last 150 years. Recently, the information in these papers has been synthesized into a picture of central nervous system (CNS) “glymphatics,” but the fine structure of lymphatic elements in the human brain based on imaging specific markers of lymphatic endothelium has not been described. We used LYVE1 and PDPN antibodies to visualize lymphatic marker-positive cells (LMPCs) in postmortem human brain samples, meninges, cavernous sinus (cavum trigeminale), and cranial nerves and bolstered our findings with a VEGFR3 antibody. LMPCs were present in the perivascular space, the walls of small and large arteries and veins, the media of large vessels along smooth muscle cell membranes, and the vascular adventitia. Lymphatic marker staining was detected in the pia mater, in the arachnoid, in venous sinuses, and among the layers of the dura mater. There were many LMPCs in the perineurium and endoneurium of cranial nerves. Soluble waste may move from the brain parenchyma via perivascular and paravascular routes to the closest subarachnoid space and then travel along the dura mater and/or cranial nerves. Particulate waste products travel along the laminae of the dura mater toward the jugular fossa, lamina cribrosa, and perineurium of the cranial nerves to enter the cervical lymphatics. CD3-positive T cells appear to be in close proximity to LMPCs in perivascular/perineural spaces throughout the brain. Both immunostaining and qPCR confirmed the presence of adhesion molecules in the CNS known to be involved in T cell migration.

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Identification and prioritization of gene sets associated with schizophrenia risk by co-expression network analysis in human brain

10.1101/286559 ◽

2018 ◽

Author(s):

Eugenia Radulescu ◽

Andrew E Jaffe ◽

Richard E Straub ◽

Qiang Chen ◽

Joo Heon Shin ◽

...

Keyword(s):

Network Analysis ◽

Human Brain ◽

Drug Targets ◽

External Validation ◽

Risk Scores ◽

Therapeutic Drug ◽

Postmortem Human Brain ◽

Polygenic Risk ◽

Gene Sets ◽

The Brain

AbstractSchizophrenia polygenic risk is plausibly manifested by complex transcriptional dysregulation in the brain, involving networks of co-expressed and functionally related genes. The main purpose of this study was to identify and prioritize co-expressed gene sets in a hierarchical manner, based on the strength of the relationships with clinical diagnosis and with the polygenic risk for schizophrenia. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to RNA-quality adjusted DLPFC RNA-Seq data from the LIBD Postmortem Human Brain Repository (90 controls, 74 schizophrenia; Caucasians) to construct co-expression networks and detect modules of co-expressed genes. After internal and external validation, modules of selected interest were tested for enrichment in biological ontologies, association with schizophrenia polygenic risk scores (PRS), with diagnosis and for enrichment in genes within the significant GWAS loci reported by the Psychiatric Genomic Consortium (PGC2). The association between schizophrenia genetic signals and modules of co-expression converged on one module showing a significant association with diagnosis, PRS and significant overlap with 36 PGC2 loci genes, deemed as tier 1 (strongest candidates for drug targets). Fifty-three PGC2 loci genes were in modules associated only with diagnosis (tier 2) and 59 in modules unrelated to diagnosis or PRS (tier 3). In conclusion, our study highlights complex relationships between gene co-expression networks in the brain and polygenic risk for SCZ and provides a strategy for using this information in selecting potentially targetable gene sets for therapeutic drug development.

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Frontier concept of rabi chip for intelligent humanoid

Journal of Analytical Chromatography and Spectroscopy ◽

10.24294/jacs.v1i2.908 ◽

2018 ◽

Vol 1 (2) ◽

Author(s):

Preecha Yupapin ◽

Amiri I. S. ◽

Ali J. ◽

Ponsuwancharoen N. ◽

Youplao P.

Keyword(s):

Human Brain ◽

Brain Function ◽

Rabi Oscillation ◽

Liquid Core ◽

Brain Surface ◽

Dipole Oscillation ◽

On Chip ◽

The Brain ◽

Robotic Applications ◽

Atom System

The sequence of the human brain can be configured by the originated strongly coupling fields to a pair of the ionic substances(bio-cells) within the microtubules. From which the dipole oscillation begins and transports by the strong trapped force, which is known as a tweezer. The tweezers are the trapped polaritons, which are the electrical charges with information. They will be collected on the brain surface and transport via the liquid core guide wave, which is the mixture of blood content and water. The oscillation frequency is called the Rabi frequency, is formed by the two-level atom system. Our aim will manipulate the Rabi oscillation by an on-chip device, where the quantum outputs may help to form the realistic human brain function for humanoid robotic applications.

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TIMELESS BUILDINGS AND THE HUMAN BRAIN: The Effect of Spiritual Spaces on Human Brain Waves

International Journal of Architectural Research Archnet-IJAR ◽

10.26687/archnet-ijar.v8i1.329 ◽

2014 ◽

Vol 8 (1) ◽

pp. 133

Author(s):

Sally M. Essawy ◽

Basil Kamel ◽

Mohamed S. Elsawy

Keyword(s):

Human Brain ◽

Case Studies ◽

Spiritual Experience ◽

Brain Wave ◽

Human Comfort ◽

Beliefs And Practices ◽

Brain Waves ◽

Space Design ◽

State Of Mind ◽

The Brain

Some buildings hold certain qualities of space design similar to those originated from nature in harmony with its surroundings. These buildings, mostly associated with religious beliefs and practices, allow for human comfort and a unique state of mind. This paper aims to verify such effect on the human brain. It concentrates on measuring brain waves when the user is located in several spots (coordinates) in some of these buildings. Several experiments are conducted on selected case studies to identify whether certain buildings affect the brain wave frequencies of their users or not. These are measured in terms of Brain Wave Frequency Charts through EEG Device. The changes identified on the brain were then translated into a brain diagram that reflects the spiritual experience all through the trip inside the selected buildings. This could then be used in architecture to enhance such unique quality.

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Art and the Brain’s Reward System

10.1093/oso/9780190927929.003.0008 ◽

2018 ◽

Author(s):

Henrik Hogh-Olesen

Keyword(s):

Human Brain ◽

Reward System ◽

Human Existence ◽

Brain Scans ◽

System P ◽

The Aesthetic ◽

The Brain ◽

Reward Circuit

Chapter 7 takes the investigation of the aesthetic impulse into the human brain to understand, first, why only we—and not our closest relatives among the primates—express ourselves aesthetically; and second, how the brain reacts when presented with aesthetic material. Brain scans are less useful when you are interested in the Why of aesthetic behavior rather than the How. Nevertheless, some brain studies have been ground-breaking, and neuroaesthetics offers a pivotal argument for the key function of the aesthetic impulse in human lives; it shows us that the brain’s reward circuit is activated when we are presented with aesthetic objects and stimuli. For why reward a perception or an activity that is evolutionarily useless and worthless in relation to human existence?

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Is There a Brain Microbiome?

Neuroscience Insights ◽

10.1177/26331055211018709 ◽

2021 ◽

Vol 16 ◽

pp. 263310552110187

Author(s):

Christopher D Link

Keyword(s):

Animal Models ◽

Human Brain ◽

Neurodegenerative Diseases ◽

Ground Truth ◽

Healthy Human ◽

Strong Motivation ◽

The Many ◽

The Brain

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome.”

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A bigger brain for a more complex environment

Reviews in the Neurosciences ◽

10.1515/revneuro-2020-0041 ◽

2020 ◽

Vol 31 (8) ◽

pp. 803-816

Author(s):

Umberto di Porzio

Keyword(s):

Human Brain ◽

Cognitive Abilities ◽

Molecular Genetic ◽

Adult Size ◽

Genetic Changes ◽

Cultural Challenges ◽

Birth Canal ◽

Newborn Brain ◽

Neuronal Interactions ◽

The Brain

AbstractThe environment increased complexity required more neural functions to develop in the hominin brains, and the hominins adapted to the complexity by developing a bigger brain with a greater interconnection between its parts. Thus, complex environments drove the growth of the brain. In about two million years during hominin evolution, the brain increased three folds in size, one of the largest and most complex amongst mammals, relative to body size. The size increase has led to anatomical reorganization and complex neuronal interactions in a relatively small skull. At birth, the human brain is only about 20% of its adult size. That facilitates the passage through the birth canal. Therefore, the human brain, especially cortex, develops postnatally in a rich stimulating environment with continuous brain wiring and rewiring and insertion of billions of new neurons. One of the consequence is that in the newborn brain, neuroplasticity is always turned “on” and it remains active throughout life, which gave humans the ability to adapt to complex and often hostile environments, integrate external experiences, solve problems, elaborate abstract ideas and innovative technologies, store a lot of information. Besides, hominins acquired unique abilities as music, language, and intense social cooperation. Overwhelming ecological, social, and cultural challenges have made the human brain so unique. From these events, as well as the molecular genetic changes that took place in those million years, under the pressure of natural selection, derive the distinctive cognitive abilities that have led us to complex social organizations and made our species successful.

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Tackling Dysfunction of Mitochondrial Bioenergetics in the Brain

International Journal of Molecular Sciences ◽

10.3390/ijms22158325 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8325

Author(s):

Paola Zanfardino ◽

Stefano Doccini ◽

Filippo M. Santorelli ◽

Vittoria Petruzzella

Keyword(s):

Human Brain ◽

Basic Function ◽

Mitochondrial Proteome ◽

Novel Proteins ◽

Mitochondrial Functions ◽

Organ Specific ◽

Oxphos System ◽

Mitochondrial Defects ◽

Energy Dependent ◽

The Brain

Oxidative phosphorylation (OxPhos) is the basic function of mitochondria, although the landscape of mitochondrial functions is continuously growing to include more aspects of cellular homeostasis. Thanks to the application of -omics technologies to the study of the OxPhos system, novel features emerge from the cataloging of novel proteins as mitochondrial thus adding details to the mitochondrial proteome and defining novel metabolic cellular interrelations, especially in the human brain. We focussed on the diversity of bioenergetics demand and different aspects of mitochondrial structure, functions, and dysfunction in the brain. Definition such as ‘mitoexome’, ‘mitoproteome’ and ‘mitointeractome’ have entered the field of ‘mitochondrial medicine’. In this context, we reviewed several genetic defects that hamper the last step of aerobic metabolism, mostly involving the nervous tissue as one of the most prominent energy-dependent tissues and, as consequence, as a primary target of mitochondrial dysfunction. The dual genetic origin of the OxPhos complexes is one of the reasons for the complexity of the genotype-phenotype correlation when facing human diseases associated with mitochondrial defects. Such complexity clinically manifests with extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. Finally, we briefly discuss the future directions of the multi-omics study of human brain disorders.

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Phenylalanine Metabolism is Dysregulated in Human Hippocampus with Alzheimer’s Disease Related Pathological Changes

Journal of Alzheimer s Disease ◽

10.3233/jad-210461 ◽

2021 ◽

pp. 1-14

Author(s):

Pan Liu ◽

Qian Yang ◽

Ning Yu ◽

Yan Cao ◽

Xue Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Human Brain ◽

Pathological Examination ◽

Pathological Changes ◽

Targeted Metabolomics ◽

Phenylpyruvic Acid ◽

Postmortem Human Brain ◽

Metabolic Dysregulation ◽

Phenylalanine Metabolism

Background: Alzheimer’s disease (AD) is one of the most challenging diseases causing an increasing burden worldwide. Although the neuropathologic diagnosis of AD has been established for many years, the metabolic changes in neuropathologic diagnosed AD samples have not been fully investigated. Objective: To elucidate the potential metabolism dysregulation in the postmortem human brain samples assessed by AD related pathological examination. Methods: We performed untargeted and targeted metabolomics in 44 postmortem human brain tissues. The metabolic differences in the hippocampus between AD group and control (NC) group were compared. Results: The results show that a pervasive metabolic dysregulation including phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis, biotin metabolism, and purine metabolism are associated with AD pathology. Targeted metabolomics reveal that phenylalanine, phenylpyruvic acid, and N-acetyl-L-phenylalanine are upregulated in AD samples. In addition, the enzyme IL-4I1 catalyzing transformation from phenylalanine to phenylpyruvic acid is also upregulated in AD samples. Conclusion: There is a pervasive metabolic dysregulation in hippocampus with AD-related pathological changes. Our study suggests that the dysregulation of phenylalanine metabolism in hippocampus may be an important pathogenesis for AD pathology formation.

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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.

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