ABCA8 stimulates sphingomyelin production in oligodendrocytes

2013 ◽  
Vol 452 (3) ◽  
pp. 401-410 ◽  
Author(s):  
Woojin Scott Kim ◽  
Jen-Hsiang T. Hsiao ◽  
Surabhi Bhatia ◽  
Elias N. Glaros ◽  
Anthony S. Don ◽  
...  
Keyword(s):  
Human Brain ◽  
Human Life ◽  
Functional Study ◽  
Peripheral Tissues ◽  
Sphingomyelin Synthase ◽  
Multiple Regions ◽  
Cortical Regions ◽  
Human Brains ◽  
The Impact ◽  
The Brain

Members of the ABCA (ATP-binding cassette subfamily A) family are characterized by their ability to transport lipids across cellular membranes and regulate lipid homoeostasis in the brain and peripheral tissues. ABCA8 is a little-known member of this subfamily that was originally cloned from human brain libraries and has no known function. In an effort to elucidate the role of ABCA8 in the brain we first undertook a comprehensive analysis of its expression in the human brain. ABCA8 was differentially expressed in multiple regions of adult human brains with significantly higher expression in oligodendrocyte-enriched white matter regions compared with grey matter cortical regions. We then assessed the impact of ABCA8 on sphingomyelin production in oligodendrocyte and showed that ABCA8 was able to significantly stimulate both sphingomyelin synthase 1 expression and sphingomyelin production. Furthermore, ABCA8 expression in the prefrontal cortex across the human life span correlated strongly with age-associated myelination, and the myelinating gene p25α was significantly up-regulated with ABCA8. The present study represents the first extensive expression and functional study of ABCA8 in the human brain and the results strongly suggest that ABCA8 regulates lipid metabolism in oligodendrocytes and potentially plays a role in myelin formation and maintenance.

Modeling the dose distribution in a human brain structure using CT images on the surface of Mars

2020 ◽  
Author(s):  
Salman Khaksarighiri ◽  
Jingnan Guo ◽  
Robert Wimmer-Schweingruber ◽  
Lennart Rostl
Keyword(s):  
Radiation Dose ◽  
Human Brain ◽  
Brain Structure ◽  
Dose Distribution ◽  
Cosmic Radiation ◽  
Cosmic Ray ◽  
Ct Images ◽  
Human Brains ◽  
The Impact ◽  
The Brain

<p>One of the most important steps in the near-future space age will be a manned mission to Mars. Unfortunately, such a mission will cause astronauts to be exposed to unavoidable cosmic radiation in deep space and on the surface of Mars. Thus a better understanding of the radiation environment for a Mars mission and the consequent biological impacts on humans, in particular the human brains, is critical. To investigate the impact of cosmic radiation on human brains and the potential influence on the brain functions, we model and study the cosmic particle-induced radiation dose in a realistic head structure. Specifically speaking, 134 slices of computed tomography (CT) images of an actual human head have been used as a 3D phantom in Geant4 (GEometry ANd Tracking) which is a Monte Carlo tool simulating energetic particles impinging into different parts of the brain and deliver radiation dose therein. As a first step, we compare the influence of different brain structures (e.g., with or without bones, with or without soft tissues) to the resulting dose therein to demonstrate the necessity of using a realistic brain structure for our investigation. Afterwards, we calculate energy-dependent functions of dose distribution for the most important (most abundant and most biologically-relevant) particle types encountered in space and on Mars such as protons, Helium ions and neutrons. These functions are then used to fold with Galactic Cosmic Ray (GCR) spectra on the surface of Mars for obtaining the dose rate distribution at different lobes of the human brain. Different GCR spectra during various solar cycle conditions have also been studied and compared.</p>

BIOLOGICAL AGE ESTIMATION BASED ON THE SPECTRAL ANALYSIS OF THE HUMAN BRAIN BIOELECTRIC ACTIVITY

2021 ◽  
pp. 466-471
Author(s):  
Г. А. Шабанов ◽  
А. А. Рыбченко ◽  
Е. А. Луговая ◽  
С.И. Вдовенко
Keyword(s):  
Spectral Analysis ◽  
Human Brain ◽  
Research Work ◽  
Risk Groups ◽  
Healthy People ◽  
Biological Age ◽  
Bioelectric Activity ◽  
Peripheral Tissues ◽  
Oncological Patients ◽  
The Brain

В работе впервые предложен способ оценки биологического возраста человека на основе спектрального анализа биоэлектрической активности головного мозга. Был разработан индекс децентрализации (IDC), который учитывал суммарную степень снижения фоновых нейротрофических влияний активирующей системы мозга на периферические ткани и органы. Получена близкая к линейной зависимость величины индекса IDC от возраста практически здоровых людей 10-90 лет и степени дифференцировки раковых клеток G1 G4 у онкологических пациентов. Накопление клеточных нарушений и мутаций с возрастом отражалось в увеличении индекса IDC от 100 до 900 у. е. Еще большее количество клеточных мутаций у онкологических пациентов со степенью дифференцировки клеток от G1 до G4 приводило к увеличению IDC до 3 000 у. е. и более. Полученные данные позволили проводить оценку биологического возраста после 10-минутной регистрации биоэлектрической активности головного мозга человека. Достоверность оценки повышалась при усреднении нескольких данных у одного человека. Технология полезна для научных исследований в области геронтологии, при мониторинге состояния практически здоровых людей, формирования групп риска и контроля лечебного процесса у онкологических пациентов. For the first time, the research work offers a method of estimating human biological age based on the spectral analysis of the brain bioelectric activity. IDC decentralization index, which could consider summary degree of reduction of the background neurotrophic influences of the brain activating system on the peripheral tissues and organs, was developed. The close to linear dependence of the IDC index on the age of healthy people aged 10-90 as well as on the oncological patients cancer G 1 G 4 cells differentiation was obtained. The cell disorders and mutations in relation with the age from 10 to 90 could be seen in growth of the IDC index from 100 to 900 units. The greater amount of the cell mutations in the oncological patients with the G 1 G 4 differentiation resulted in the IDC index growth up to the 3 000 units and more. All the obtained data allowed estimating the real biological age after a 10-minute registration of the human brain bioelectric activity. The accuracy increased with the averaging several surveys taken from one particular person. The technology will be highly efficient for scientific researches in the field of gerontology, monitoring of healthy people, revealing of risk groups, and for controlling of the cancer patients medical treatment.

Epigenetics in Psychiatry

2018 ◽  
pp. 165-183
Author(s):  
Subha Subramanian ◽  
James B. Potash
Keyword(s):  
Dna Methylation ◽  
Human Brain ◽  
Psychiatric Disorders ◽  
Drugs Of Abuse ◽  
Future Directions ◽  
Peripheral Tissues ◽  
Risk Genes ◽  
Epigenetic Biomarkers ◽  
Ongoing Work ◽  
The Impact

Epigenetic modifications such as DNA methylation (DNAm), histone acetylation and methylation, and those directed by small RNAs, are widely studied in psychiatry and may play a role in the etiology and pathophysiology of psychiatric disorders. This chapter provides a brief overview of the mechanisms regulating these epigenetic marks and the challenges in obtaining biologically meaningful epigenetic data, given the inaccessibility of the living human brain. Significant results to date from studies on the epigenetics of psychiatric disorders are presented, including the impact of stress on DNAm in psychiatric risk genes such as FKBP5, and the impact of drugs of abuse and of psychiatric medications on histone modifications. Future directions are discussed, including the study of newly discovered aspects of DNAm: 5-hydroxymethylcytosine and non-CpG methylation. Ongoing work aims to uncover neurobiological mechanisms of illness and to find epigenetic biomarkers in peripheral tissues that inform diagnosis, prognosis, and therapeutic response.

Mental illness: The collision of meaning with mechanism

2020 ◽  
pp. 263-289
Author(s):  
Steven E. Hyman ◽  
Doug McConnell
Keyword(s):  
Mental Illness ◽  
Gene Regulation ◽  
Human Brain ◽  
Lived Experience ◽  
Clinical Encounter ◽  
Structure And Function ◽  
Human Beings ◽  
And Function ◽  
Human Brains ◽  
The Brain

‘Mental illness: the collision of meaning with mechanism’ is based on the views of psychiatry that Steven Hyman articulated in his Loebel Lectures—mental illness results from the disordered functioning of the human brain and effective treatment repairs or mitigates those malfunctions. This view is not intended as reductionist as causes of mental illness and contributions to their repair may come from any source that affects the structure and function of the brain. These might include social interactions and other sources of lived experience, ideas (such as those learned in cognitive therapy), gene sequences and gene regulation, metabolic factors, drugs, electrodes, and so on. This, however, is not the whole story for psychiatry on Hyman’s view; interpersonal interactions between clinicians and patients, intuitively understood in such folk psychological terms as selfhood, intention, and agency are also critical for successful practice. As human beings who are suffering, patients seek to make sense of their lives and benefit from the empathy, respect, and a sense of being understood not only as the objects of a clinical encounter, but also as subjects. Hyman’s argument, however, is that the mechanisms by which human brains function and malfunction to produce the symptoms and impairments of mental illness are opaque to introspection and that the mechanistic understandings necessary for diagnosis and treatment are incommensurate with intuitive (folk psychological) human self-understanding. Thus, psychiatry does best when skillful clinicians switch between an objectifying medical and neurobiological stance and the interpersonal stance in which the clinician engages the patients as a subject. Attempts to integrate these incommensurate views of patients and their predicaments have historically produced incoherent explanations of psychopathology and have often led treatment astray. For example, privileging of folk psychological testimony, even when filtered through sophisticated theories has historically led psychiatry into intellectually blind and clinically ineffective cul-de-sacs such as psychoanalysis.

scholarly journals Associations of Vitamin D and Vitamin K and Their Metabolites Across Four Regions of the Human Brain: The Memory and Aging Project (MAP) (FS05-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Xueyan Fu ◽  
Will Patterson ◽  
Gregory Dolnikowski ◽  
Bess Dawson-Hughes ◽  
Martha Morris ◽  
...  
Keyword(s):  
Vitamin D ◽  
Human Brain ◽  
Vitamin K ◽  
Vitamin D3 ◽  
Rank Order ◽  
Temporal Cortex ◽  
Correlation Coefficients ◽  
Brain Regions ◽  
Multiple Regions ◽  
The Brain

Abstract Objectives Very little is known about the forms of vitamin D and vitamin K in the human brain. The objective of this study is to evaluate concentrations of vitamin D and vitamin K forms in human brain and their correlations across four human brain regions. Methods Vitamin D [D3, 25(OH)D and 1,25(OH)2D] and vitamin K [phylloquinone and menaquinone-4 (MK4)] concentrations were measured by LC/MS/MS and HPLC, respectively, in four brain regions from post-mortem samples obtained from participants in the Rush Memory and Aging Project (n = 130, mean age 82 yrs, 81% female). The brain regions analyzed were the mid-frontal cortex (MF) and mid-temporal cortex (MT) [two regions important for memory in Alzheimer's Disease (AD)], the cerebellum (CR, a region not affected by AD), and the anterior watershed white matter (AWS, a region associated with vascular disease). The correlations among the vitamin forms across brain regions were calculated using Spearman rank order correlation coefficients. Significance was set at P < 0.001. Results The average concentrations of vitamin D3, 25(OH)D and MK4 were 604 pg/g, 535 pg/g, and 3.4 pmol/g, respectively. 25(OH)D and MK4 were detected in >95% of the brain samples. Nearly 92% of 1,25(OH)2D and 80% of phylloquinone samples had concentrations below the limit of assay detection (LOD) 1,25(OH)2D = 20 ng/g, phylloquinone = 0.1 pmol/g). Vitamin D3 and 25(OH)D concentrations were positively correlated across all four regions (all Spearman r ≥ 0.78, P < 0.0001). The 1,25(OH)2D was significantly correlated between the MF and CR regions only (Spearman r = 0.30, P < 0.001, all other P ≥ 0.002). MK4 and PK were positively correlated across the four regions studied (MK4 all Spearman r ≥ 0.78, phylloquinone r ≥ 0.49, all P < 0.001). Conclusions To the best of our knowledge, this study is the first evaluation of the concentrations of vitamin D and vitamin K forms in multiple regions of the human brain. Overall, the vitamin D and vitamin K forms were each positively correlated across the four brain regions studied. Future studies are needed to clarify the roles of these nutrients in AD and dementia. Funding Sources National Institute of Aging.

scholarly journals Facephenes and rainbows: Causal evidence for functional and anatomical specificity of face and color processing in the human brain

2017 ◽  
Vol 114 (46) ◽  
pp. 12285-12290 ◽  
Author(s):  
Gerwin Schalk ◽  
Christoph Kapeller ◽  
Christoph Guger ◽  
Hiroshi Ogawa ◽  
Satoru Hiroshima ◽  
...  
Keyword(s):  
Human Brain ◽  
Mental Process ◽  
Color Processing ◽  
Face Area ◽  
Neurosurgical Patient ◽  
Patient Reported ◽  
Stimulus Classes ◽  
Cortical Regions ◽  
The Brain

Neuroscientists have long debated whether some regions of the human brain are exclusively engaged in a single specific mental process. Consistent with this view, fMRI has revealed cortical regions that respond selectively to certain stimulus classes such as faces. However, results from multivoxel pattern analyses (MVPA) challenge this view by demonstrating that category-selective regions often contain information about “nonpreferred” stimulus dimensions. But is this nonpreferred information causally relevant to behavior? Here we report a rare opportunity to test this question in a neurosurgical patient implanted for clinical reasons with strips of electrodes along his fusiform gyri. Broadband gamma electrocorticographic responses in multiple adjacent electrodes showed strong selectivity for faces in a region corresponding to the fusiform face area (FFA), and preferential responses to color in a nearby site, replicating earlier reports. To test the causal role of these regions in the perception of nonpreferred dimensions, we then electrically stimulated individual sites while the patient viewed various objects. When stimulated in the FFA, the patient reported seeing an illusory face (or “facephene”), independent of the object viewed. Similarly, stimulation of color-preferring sites produced illusory “rainbows.” Crucially, the patient reported no change in the object viewed, apart from the facephenes and rainbows apparently superimposed on them. The functional and anatomical specificity of these effects indicate that some cortical regions are exclusively causally engaged in a single specific mental process, and prompt caution about the widespread assumption that any information scientists can decode from the brain is causally relevant to behavior.

scholarly journals “Neurocovid”: An Analysis of the Impact of Covid-19 on the Older Adults. Evolving Psychological and Neuropsychological Understanding

2021 ◽  
Author(s):  
Sara Palermo
Keyword(s):  
Older Adults ◽  
Nervous System ◽  
Adverse Effects ◽  
Human Brain ◽  
The Elderly ◽  
Cognitive Frailty ◽  
Daily Routines ◽  
The Impact ◽  
The Brain

When SARS-CoV-2 began to spread, older adults experienced disproportionately greater adverse effects from the pandemic, including exacerbation of pre-existing physical and cognitive frailty conditions. More severe complications, higher mortality, and concerns about disruptions to their daily routines and access to care. Knowledge about the impact of COVID-19 on the brain is rapidly accumulating and this is reflected in the increasing use of the term “neurocovid”. Co-involvement of the central and peripheral nervous system had already been observed in SARS patients, but COVID-19 seems to invade it with greater affinity than other coronaviruses. This chapter provides an overview of the expanding understanding of the multiple ways in which COVID-19 affects the human brain, discuss the likelihood of long-term sequelae of neurocovid, and their implications for cognitive functions and behaviors in the elderly.

scholarly journals Human Development XIII: The Connection Between the Structure of the Overtone System and the Tone Language of Music. Some Implications for Our Understanding of the Human Brain

2008 ◽  
Vol 8 ◽  
pp. 643-657 ◽  
Author(s):  
Søren Ventegodt ◽  
Tyge Dahl Hermansen ◽  
Isack Kandel ◽  
Joav Merrick
Keyword(s):  
Human Brain ◽  
Human Life ◽  
Quantum Field ◽  
Positive Experience ◽  
Tone Language ◽  
Quantum Reality ◽  
Major Scale ◽  
Life Itself ◽  
Language Of Music ◽  
The Brain

The functioning brain behaves like one highly-structured, coherent, informational field. It can be popularly described as a “coherent ball of energy”, making the idea of a local highly-structured quantum field that carries the consciousness very appealing. If that is so, the structure of the experience of music might be a quite unique window into a hidden quantum reality of the brain, and even of life itself. The structure of music is then a mirror of a much more complex, but similar, structure of the energetic field of the working brain. This paper discusses how the perception of music is organized in the human brain with respect to the known tone scales of major and minor. The patterns used by the brain seem to be similar to the overtones of vibrating matter, giving a positive experience of harmonies in major. However, we also like the minor scale, which can explain brain patterns as fractal-like, giving a symmetric “downward reflection” of the major scale into the minor scale. We analyze the implication of beautiful and ugly tones and harmonies for the model. We conclude that when it comes to simple perception of harmonies, the most simple is the most beautiful and the most complex is the most ugly, but in music, even the most disharmonic harmony can be beautiful, if experienced as a part of a dynamic release of musical tension. This can be taken as a general metaphor of painful, yet meaningful, and developing experiences in human life.

scholarly journals Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy

2019 ◽  
Vol 12 (3) ◽  
pp. 120 ◽  
Author(s):  
Veronika Markova ◽  
Charlotte Holm ◽  
Anja Pinborg ◽  
Lars Thomsen ◽  
Torben Moos
Keyword(s):  
Iron Deficiency ◽  
Human Brain ◽  
Human Life ◽  
Later Life ◽  
Developing Brain ◽  
Receptor Expression ◽  
Cellular Functions ◽  
Iron Extraction ◽  
Experimental Animals ◽  
The Brain

Due to the necessity of iron for a variety of cellular functions, the developing mammalian organism is vulnerable to iron deficiency, hence causing structural abnormalities and physiological malfunctioning in organs, which are particularly dependent on adequate iron stores, such as the brain. In early embryonic life, iron is already needed for proper development of the brain with the proliferation, migration, and differentiation of neuro-progenitor cells. This is underpinned by the widespread expression of transferrin receptors in the developing brain, which, in later life, is restricted to cells of the blood–brain and blood–cerebrospinal fluid barriers and neuronal cells, hence ensuring a sustained iron supply to the brain, even in the fully developed brain. In embryonic human life, iron deficiency is thought to result in a lower brain weight, with the impaired formation of myelin. Studies of fully developed infants that have experienced iron deficiency during development reveal the chronic and irreversible impairment of cognitive, memory, and motor skills, indicating widespread effects on the human brain. This review highlights the major findings of recent decades on the effects of gestational and lactational iron deficiency on the developing human brain. The findings are correlated to findings of experimental animals ranging from rodents to domestic pigs and non-human primates. The results point towards significant effects of iron deficiency on the developing brain. Evidence would be stronger with more studies addressing the human brain in real-time and the development of blood biomarkers of cerebral disturbance in iron deficiency. Cerebral iron deficiency is expected to be curable with iron substitution therapy, as the brain, privileged by the cerebral vascular transferrin receptor expression, is expected to facilitate iron extraction from the circulation and enable transport further into the brain.

A Case Study on EEG Analysis: Embedding Entropy Estimations Indicate the Decreased Neuro-Cortical Complexity Levels Mediated by Methylphenidate Treatment in Children With ADHD

2021 ◽  
pp. 155005942110640
Author(s):  
Fatih Hilmi Çetin ◽  
Miraç Barış Usta ◽  
Serap Aydın ◽  
Ahmet Sami Güven
Keyword(s):  
Complexity Analysis ◽  
Approximate Entropy ◽  
Quantitative Eeg ◽  
Symptom Cluster ◽  
Permutation Entropy ◽  
Eeg Analysis ◽  
Pre Treatment ◽  
Cortical Regions ◽  
The Impact ◽  
The Brain

Objective: Complexity analysis is a method employed to understand the activity of the brain. The effect of methylphenidate (MPH) treatment on neuro-cortical complexity changes is still unknown. This study aimed to reveal how MPH treatment affects the brain complexity of children with attention deficit hyperactivity disorder (ADHD) using entropy-based quantitative EEG analysis. Three embedding entropy approaches were applied to short segments of both pre- and post- medication EEG series. EEG signals were recorded for 25 boys with combined type ADHD prior to the administration of MPH and at the end of the first month of the treatment. Results: In comparison to Approximate Entropy (ApEn) and Sample Entropy (SampEn), Permutation Entropy (PermEn) provided the most sensitive estimations in investigating the impact of MPH treatment. In detail, the considerable decrease in EEG complexity levels were observed at six cortical regions (F3, F4, P4, T3, T6, O2) with statistically significant level ( p < .05). As well, PermEn provided the most meaningful associations at central lobes as follows: 1) The largeness of EEG complexity levels was moderately related to the severity of ADHD symptom detected at pre-treatment stage. 2) The percentage change in the severity of opposition as the symptom cluster was moderately reduced by the change in entropy. Conclusion: A significant decrease in entropy levels in the frontal region was detected in boys with combined type ADHD undergoing MPH treatment at resting-state mode. The changes in entropy correlated with pre-treatment general symptom severity of ADHD and conduct disorder symptom cluster severity.

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