MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer

The mammalian brain is made up of billions of neurons and supporting cells (glial cells), intricately connected. Molecular perturbations often lead to neurodegeneration by progressive loss of structure and malfunction of neurons, including their death. On the other side, a combination of genetic and cellular factors in glial cells, and less frequently in neurons, drive oncogenic transformation. In both situations, microenvironmental niches influence the progression of diseases and therapeutic responses. Dynamic changes that occur in cellular transcriptomes during the progression of developmental lineages and pathogenesis are controlled through a variety of regulatory networks. These include epigenetic modifications, signaling pathways, and transcriptional and post-transcriptional mechanisms. One prominent component of the latter is small non-coding RNAs, including microRNAs, that control the vast majority of these networks including genes regulating neural stemness, differentiation, apoptosis, projection fates, migration and many others. These cellular processes are also profoundly dependent on the microenvironment, stemness niche, hypoxic microenvironment, and interactions with associated cells including endothelial and immune cells. Significantly, the brain of all other mammalian organs expresses the highest number of microRNAs, with an additional gain in expression in the early stage of neurodegeneration and loss in expression in oncogenesis. However, a mechanistic explanation of the concept of an apparent inverse correlation between the odds of cancer and neurodegenerative diseases is only weakly developed. In this review, we thus will discuss widespread de-regulation of microRNAome observed in these two major groups of brain pathologies. The deciphering of these intricacies is of importance, as therapeutic restoration of pre-pathological microRNA landscape in neurodegeneration must not lead to oncogenesis and vice versa. We thus focus on microRNAs engaged in cellular processes that are inversely regulated in these diseases. We also aim to define the difference in microRNA networks between pro-survival and pro-apoptotic signaling in the brain.

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Expression of macrophage CD14 receptor in the course of experimental inflammatory responses induced by lipopolysaccharide and muramyl dipeptide

Veterinární Medicína ◽

10.17221/1991-vetmed ◽

2008 ◽

Vol 53 (No. 7) ◽

pp. 347-357 ◽

Cited By ~ 4

Author(s):

Z. Sladek ◽

D. Rysanek

Keyword(s):

Inflammatory Response ◽

Inflammatory Responses ◽

Early Stage ◽

Muramyl Dipeptide ◽

Cell Suspensions ◽

The Other ◽

Total Count ◽

The Difference ◽

Phosphate Buffered Saline ◽

Time Point

The aim of this study was to determine whether expression of CD14 on macrophages is regulated differently during initiation and resolution of the inflammatory response caused by CD14-dependent (lipopolysaccharide) and CD14-independent (muramyldipeptide) bacterial signals. In cell suspensions from the site of inflammation we observed two types of macrophages: non-vacuolized (NMAC) and vacuolized (VMAC) cells. NMAC (monocyte-like cells) were dominant during the early stage of the inflammatory response, whilst VMAC contained phagocytosed apoptotic neutrophils in various stages of digestion. These latter cells were dominant during resolution (particularly at the last time point of 168 h). Intramammary instillation of muramyldipeptide (MDP) and lipopolysaccharide (LPS) resulted in a significant increase in the total count of CD14+ NMAC after 24 h (muramyldipeptide P < 0.01 and lipopolysaccharide P < 0.05) compared to phosphate buffered saline (PBS). During resolution of the inflammatory response, a gradual decrease in the total count of CD14+ NMAC was observed. The difference compared with PBS was significant at 48 h and 72 h after instillation of both bacterial agents (muramyldipeptide: P < 0.05; lipopolysaccharide: P < 0.05). A lower total count of CD14+ VMAC was observed as an effect of MDP and LPS at 24 h after induction (P < 0.05), when compared to PBS. During resolution, the total count of CD14+ VMAC increased. Differences (P < 0.01) were observed at 72 h and 168 h after LPS compared to PBS. We therefore assume that the expression of CD14 on macrophages is not regulated differently during the inflammatory responses caused by CD14-dependent and CD14-independent bacterial signals. On the other hand, the stage of the inflammatory response to MDP and LPS played an important role in the regulation of CD14 expression on macrophages.

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Ordering Disorder

10.1093/oxfordhb/9780199579563.013.0032 ◽

2013 ◽

Author(s):

George Graham

Keyword(s):

Mental Disorders ◽

Mental Disorder ◽

Type A ◽

The Other ◽

Brain Disorder ◽

The Difference ◽

The One ◽

The Brain

The basic claims of the chapter are, first, that mental disorders are not best understood as types of brain disorder, even though mental disorders are based in the brain. And, second, that the difference between the two sorts of disorders can be illuminated by the sorts of treatment or therapy that may work for the one type (a mental disorder) but not for the other type (a brain disorder). In the discussion some of the diagnostic implications and difficulties associated with these two basic claims are outlined.

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Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

10.1101/481697 ◽

2018 ◽

Cited By ~ 5

Author(s):

Linpei Zhang ◽

Yuqiu Li ◽

Wenshu Meng ◽

Yanying Ni ◽

Youhe Gao

Keyword(s):

Tumor Cells ◽

Early Stage ◽

Clinical Manifestations ◽

Tumor Model ◽

Protein Patterns ◽

Differential Proteins ◽

Walker 256 ◽

The Difference ◽

Intracerebral Tumor ◽

The Brain

AbstractPatients with primary and metastatic brain cancer have an extremely poor prognosis, mostly due to the late diagnosis of disease. Urine, which lacks homeostatic mechanisms, is an ideal biomarker source that accumulates early and highly sensitive changes to provides information about the early stage of disease. A rat model mimicking the local tumor growth process in the brain was established with intracerebral Walker 256 (W256) cell injection. Urine samples were collected on days 3, 5 and 8 after injection and then analyzed by LC-MS/MS. In the intracerebral W256 model, no obvious clinical manifestations changes or abnormal MRI signals were found on days 3 and 5; at these time points, nine proteins were changed significantly in the urine of all 8 tumor rats. On day 8, when tumors were detected by MRI, twenty-five differential proteins were identified, including 10 proteins that have been reported to be closely related to tumor metastasis or brain tumors. The differential urinary proteomes were compared with those from the subcutaneous W256 model and the intracerebral C6 model. Few differential proteins overlapped. Specific differential protein patterns were observed among the three models, indicating that the urinary proteome can reflect the difference when tumor cells with different growth characteristics are inoculated into the brain and when identical tumor cells are inoculated into different areas, specifically, the subcutis and the brain.

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The Physiology of some Phases of the Poetic Mind

Journal of Mental Science ◽

10.1017/s0368315x00009427 ◽

1878 ◽

Vol 24 (106) ◽

pp. 233-243

Author(s):

Frederick Treves

Keyword(s):

The Other ◽

Mental Processes ◽

Structural Position ◽

Correct Conclusion ◽

The Difference ◽

Experienced Physician ◽

The Mind ◽

The Brain

To take one other example as illustrating a somewhat different aspect of this question. An experienced physician arrives in a moment at the diagnosis of a case presented to his notice, but a well read and well informed student may ponder long before attaining a correct conclusion under exactly similar circumstances. In what does the difference between the mental processes in the two individuals consist? It will be said to be a matter of experience merely; but what does this statement imply? In the process of arriving at a diagnosis of the case many facts will have to be observed, many points criticised, and many arguments weighed and valued. Now in the case of the senior observer all these facts, these points, these arguments will perhaps have been passed through the mind some hundreds of times before, in reviewing similar cases; the various steps whereby his final opinion is attained will, by frequent exercise and repetition, have become separately organised in the brain, and, however rapidly his conclusion may have been arrived at, the various steps will have been undertaken. But inasmuch as their influence is exercised automatically, he remains unconscious of their agency, until he stops to analyse the various reasons that have—to a very great extent unconsciously—laid the foundations of his diagnosis and the various details on which his opinion has been founded. The process may involve no more consciousness than is displayed in the movements of the envelope folder; one is aware that the envelope is folded, and the other that he has arrived at a definite opinion; but neither may be awake to the separate steps of the process until they deliberately investigate the details of the preceding movements. In the case of the immature observer, frequent repetition has not as yet made certain processes necessary to the diagnosis of the case familiar to his mind, and in consequence they have attained no sound structural position in his nerve centres; so, like the novice in the mystery of envelope folding, he has to consider each step, and proceed with deliberation, and under the acute guardianship of consciousness.

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Study of different Carbon Bond 6 (CB6) mechanisms by using a concentration sensitivity analysis

Atmospheric Chemistry and Physics ◽

10.5194/acp-21-12687-2021 ◽

2021 ◽

Vol 21 (16) ◽

pp. 12687-12714

Author(s):

Le Cao ◽

Simeng Li ◽

Luhang Sun

Keyword(s):

Sensitivity Analysis ◽

Early Stage ◽

Reaction System ◽

The Other ◽

Peroxy Radicals ◽

Nox Formation ◽

Carbon Bond ◽

Surface Emission ◽

Concentration Sensitivity ◽

The Difference

Abstract. Since the year 2010, different versions of the Carbon Bond 6 (CB6) mechanism have been developed to accurately estimate the contribution to air pollution by the chemistry. In order to better understand the differences in simulation results brought about by the modifications between different versions of the CB6 mechanism, in the present study, we investigated the behavior of three different CB6 mechanisms (CB6r1, CB6r2 and CB6r3) in simulating ozone (O3), nitrogen oxides (NOx) and formaldehyde (HCHO) under two different emission conditions by applying a concentration sensitivity analysis in a box model. The results show that when the surface emission is weak, the O3 level predicted by CB6r1 is approximately 7 ppb higher than that predicted by CB6r2 and CB6r3, specifically due to the change in the sink of acyl peroxy radicals with high-order carbons (i.e., species CXO3) in the mechanism and the difference in the ozone dependence on the isoprene emission. In contrast, although CB6r1 estimates higher values of NOx and HCHO than the other two mechanisms at an early stage of the simulation, the levels of NOx and HCHO estimated by these three CB6 mechanisms at the end of the 7 d simulation are mostly similar, when the surface emission is weak. After the increase in the surface emission, the simulated profiles of O3, NOx and HCHO obtained by CB6r2 and CB6r3 were found to be nearly the same during the simulation period, but CB6r1 tends to estimate substantially higher values than CB6r2 and CB6r3. The deviation between the O3 levels provided by CB6r1 and the other two CB6 mechanisms (i.e., CB6r2 and CB6r3) was found to be enlarged compared with the weak-emission scenario because of the weaker dependence of ozone on the emission of isoprene in CB6r1 than those in CB6r2 and CB6r3 in this scenario. Moreover, HCHO predicted by CB6r1 was found to be larger than those predicted by CB6r2 and CB6r3, which is caused by an enhanced dependence of HCHO on the emission of isoprene in CB6r1. Regarding NOx, it was found that CB6r1 gives a higher value than the other two mechanisms, which is caused by the relatively stronger connection between the NOx prediction and the release of NO and NO2 in CB6r1 due to the change in the product of the reaction between isoprene and NO3 in CB6r1. Consequently, more emitted NOx is involved in the reaction system denoted by CB6r1, which enables a following NOx formation and thus a higher NOx prediction of CB6r1.

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In Memoriam: Ben Barres

The Journal of Cell Biology ◽

10.1083/jcb.201801019 ◽

2018 ◽

Vol 217 (2) ◽

pp. 435-438 ◽

Cited By ~ 3

Author(s):

Nicola J. Allen ◽

Richard Daneman

Keyword(s):

Pancreatic Cancer ◽

Sexual Orientation ◽

Glial Cells ◽

Scientific Community ◽

The Other ◽

Equal Treatment ◽

Indelible Mark ◽

In Memoriam ◽

The Brain

Ben Barres, professor of neurobiology at Stanford University and member of the JCB editorial board for over 15 years, passed away on December 27, 2017, after a lengthy battle with pancreatic cancer. Ben left an indelible mark on the scientific community as a scientist, an advocate for equality, and an unbelievably supportive mentor. As a scientist his creative approaches led him to remarkable discoveries about the importance of glial cells in the brain, and his passion elevated these cells from the “other cells in the brain” to a significant place in the consciousness of neurobiology. As an advocate, he fought for equal treatment irrespective of gender identity, sexual orientation, race, or ethnicity, and was an inspiring supporter of junior scientists. As a mentor, he provided a creative and vibrant atmosphere for his trainees to pursue research and the never-ending support for them to flourish as independent scientists. As his former trainees, we would like to give our thoughts on Ben, and the deep impressions that he left on everyone he interacted with.

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Nerve and Brain

Mind Shift ◽

10.1093/oso/9780198801634.003.0005 ◽

2021 ◽

pp. 63-79

Author(s):

John Parrington

Keyword(s):

Human Brain ◽

Glial Cells ◽

Large Scale ◽

Brain Size ◽

Adult Brain ◽

The Other ◽

Basic Unit ◽

The Brain ◽

Size And Structure

This chapter evaluates the basic unit of the human brain: the nerve cell, or neuron. These cells are also the main units of the peripheral nervous system, which sends messages from the brain to the other tissues and organs that make up our bodies. Neurons are the most well-known cells in the brain but they are not the only type of cell in this organ. The other main types are the glial cells, also known as neuroglia. Recent studies of the role of glial cells in the brain are revealing potentially important differences between humans and other species in the functions of these cells. The chapter then turns to the large-scale structure of the brain. The most dramatic changes in brain size and structure occurred in the final phase of human evolutionary change. Indeed, Neanderthals had brains similar in size to those of modern humans. An important feature of the human brain is that a larger fraction of its growth occurs outside the womb. Although humans reach adult brain size in childhood, brain development continues for decades afterwards.

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Critical Molecular and Cellular Contributors to Tau Pathology

Biomedicines ◽

10.3390/biomedicines9020190 ◽

2021 ◽

Vol 9 (2) ◽

pp. 190

Author(s):

Liqing Song ◽

Evan A. Wells ◽

Anne Skaja Robinson

Keyword(s):

Signaling Pathways ◽

Glial Cells ◽

Early Stage ◽

Neuronal Loss ◽

Disease Spread ◽

Tau Pathology ◽

Neuroprotective Effects ◽

Inflammatory Microenvironment ◽

Mapt Gene ◽

The Brain

Tauopathies represent a group of neurodegenerative diseases including Alzheimer’s disease (AD) that are characterized by the deposition of filamentous tau aggregates in the brain. The pathogenesis of tauopathies starts from the formation of toxic ‘tau seeds’ from hyperphosphorylated tau monomers. The presence of specific phosphorylation sites and heat shock protein 90 facilitates soluble tau protein aggregation. Transcellular propagation of pathogenic tau into synaptically connected neuronal cells or adjacent glial cells via receptor-mediated endocytosis facilitate disease spread through the brain. While neuroprotective effects of glial cells—including phagocytotic microglial and astroglial phenotypes—have been observed at the early stage of neurodegeneration, dysfunctional neuronal-glial cellular communication results in a series of further pathological consequences as the disease progresses, including abnormal axonal transport, synaptic degeneration, and neuronal loss, accompanied by a pro-inflammatory microenvironment. Additionally, the discovery of microtubule-associated protein tau (MAPT) gene mutations and the strongest genetic risk factor of tauopathies—an increase in the presence of the ε2 allele of apolipoprotein E (ApoE)—provide important clues to understanding tau pathology progression. In this review, we describe the crucial signaling pathways and diverse cellular contributors to the progression of tauopathies. A systematic understanding of disease pathogenesis provides novel insights into therapeutic targets within altered signaling pathways and is of great significance for discovering effective treatments for tauopathies.

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Determination of the Time of Death by Continuous Post-Mortem Temperature Measurements

Medicine Science and the Law ◽

10.1177/002580247701700209 ◽

1977 ◽

Vol 17 (2) ◽

pp. 112-122 ◽

Cited By ~ 29

Author(s):

Jørn Simonsen ◽

Jorgen Voigt ◽

Niels Jeppesen

Keyword(s):

Brain Temperature ◽

The Other ◽

Temperature Measurements ◽

Reliable Estimate ◽

Time Of Death ◽

Post Mortem ◽

Order Of Magnitude ◽

The Difference ◽

The Brain

In 20 cases with known times of death continuous post-mortem measurements of the temperature fall in brain, calf, liver, axilla and rectum of the bodies have been made, and, in addition, the environmental temperature has been recorded. The observations were not made under standardized conditions, and the clothing of the bodies was left untouched as far as possible. The measurements of the brain temperatures have given the greatest accuracy in determining the time of death; for temperatures above 25 °C the uncertainty was of the order of magnitude of ±2 1/2 hours, at lower temperatures greater. The other sites of measurement permitted less reliable estimates of the post-mortem time, but none of them were found to be appropriate beyond 20 hours after death. There is one factor which cannot be calculated. It is the temperature at the moment of death. All investigations show that it may vary enormously. In the present study the difference between the maximum and the minimum starting temperature ranges between 5 °C and 8 °C, dependent on the site of measurement. As the fall in temperature—irrespective of the site of measurement—during the first few hours post mortem is of the magnitude of 1 °C per hour, the above variation gives an inaccuracy which by far exceeds what can be achieved of greater accuracy by the aid of brain temperature measurements. For this reason the authors feel justified in concluding that the determination of the time of death will always be encumbered with great uncertainty, but that the most reliable estimate within the first 20 hours after death can be based upon the measurement of the brain temperature associated with an evaluation of the development of the signs of death. None of the other methods tested so far appears to have offered a greater reliability.

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