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Regulatory RNAs in the Nervous System

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194834 Year: Pages: 344 DOI: 10.3389/978-2-88919-483-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-11-16 15:44:59
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Until about a decade ago, the non-coding part of the genome was considered without function. RNA sequencing studies have shown, however, that a considerable part of the non-coding genome is transcribed and that these non-coding RNAs (nc-RNAs) can regulate gene expression. Almost on weekly basis, new findings reveal the regulatory role of nc-RNAs exert in many biological processes. Overall, these studies are making increasingly clear that, both in model organisms and in humans, complexity is not a function of the number of protein-coding genes, but results from the possibility of using combinations of genetic programs and controlling their spatial and temporal regulation during development, senescence and in disease by regulatory RNAs. This has generated a novel picture of gene regulatory networks where regulatory nc-RNAs represent novel layers of regulation. Particularly well-characterized is the role of microRNAs (miRNAs), small nc-RNAs, that bind to mRNAs and regulate gene expression after transcritpion. This message is particularly clear in the nervous system, where miRNAs have been involved in regulating cellular pathways controlling fundamental functions during development, synaptic plasticity and in neurodegenerative disease. It has also been shown that neuronal miRNAs are tightly regulated by electrical activity at the level of transcription, biogenesis, stability and specifically targeted to dendrites and synapsis. Deregulation of expression of miRNAs is proposed not only as potential disease biomarker, but it has been implicated directly in the pathogenesis of complex neurodegenerative disease. This so-called RNA revolution also lead to the exploitation of RNA interference and the development of related tools as potential treatment of a vast array of CNS disease that could benefit from regulation of disease-associated genes. In spite of these advancements, the relatively young age of this field together with the inherent high molecular complexity of RNA regulation of biological processes have somewhat hindered its communication to the whole of the neuroscience community. This Research Topic aims at improving this aspect by putting around the same virtual table scientists covering aspects ranging from basic molecular mechanisms of regulatory RNAs in the nervous system to the analysis of the role of specific regulatory RNAs in neurobiological processes of development, plasticity and aging. Furthermore, we will welcome papers analyzing the role of regulatory RNAs in disease models from neuromuscular to higher cognitive functions, and we will also encourage submission of more technically oriented papers dealing with new methodologies to study regulatory RNA biology and its translational potential.

Thyroid hormone in brain and brain cells

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197026 Year: Pages: 106 DOI: 10.3389/978-2-88919-702-6 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Thyroid hormone signaling has been known for a long time to be required for proper neurodevelopment and the maintenance of cognitive functions in the adult brain. As thyroid hormone excess or deficiency is usually well handled by clinicians, research dedicated to the neural function of thyroid hormone, have not been a priority within the field. This is changing mainly for two reasons. First, new genetic diseases have been discovered, altering thyroid hormone signaling in brain (THRA, MCT8, SBP2), with neurodevelopmental consequences which are currently incurable. Second, there is a growing concern that exposition of the general population to environmental chemicals able to interfere with thyroid hormone signaling compromises children neurodevelopment or induces central disorders in adults. Finally thyroid hormone is acting directly on gene transcription, by binding nuclear receptors, and therefore is an interesting entry point to identify genetic programs controlling brain development and function. Reaching a broad understanding of the multiple processes involving thyroid hormone in brain is a tremendous task which will necessitate a multidisciplinary approach: animal genetics, molecular biology, brain imaging, developmental biology, genomics, etc... This topic will be the occasion to combine recent contributions in the field and to identify priorities for future investigations. Due to devastating consequences of congenital hypothyroidism, the neurodevelopmental consequences of altered thyroid hormone signaling have been extensively studied over the years. The discovery of new genetic diseases, the concern about the possible neurotoxicity of environmental thyroid hormone disruptors, recently renewed the interest for an important research field. This Ebook gathers reviews and original data from experts in various disciplines. It provides a broad view of ongoing research and outlines key issues for future investigation.

Impact of Diet on Learning, Memory and Cognition

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452286 Year: Pages: 117 DOI: 10.3389/978-2-88945-228-6 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-10-13 14:57:01
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Changes in food composition and availability have contributed to the dramatic increase in obesity over the past 30-40 years in developed and, increasingly, in developing countries. The modern diet now contains many foods that are rich in saturated fat and refined sugar. People who eat excessive amounts of this diet are not only likely to become overweight, even obese, develop metabolic and cardiovascular diseases, some forms of cancer, but also undergo a more rapid rate of normal age-related cognitive decline and more rapid progression of neurological diseases such as dementia. A central problem is why people persist in consuming this diet in spite of its adverse health effects and when alternative food choices are available. As high fat / high sugar foods are inherently rewarding, eating for pleasure, like taking psychoactive drugs, can modulate reward neurocircuitry, causing changes in responsiveness to reward-predicting stimuli and incentive motivation. Indeed, the excessive ingestion in modern societies and the resulting obesity epidemic may be viewed as a form of food addiction. Thus, a diet high in palatable foods is proposed to impact upon reward systems in the brain, modulating appetitive learning and altering reward thresholds. Impairments in other forms of cognition have been associated with obesity, and these have a rapid onset. The hippocampus appears to be particularly vulnerable to the detrimental effects of high fat and high sugar diets. Recent research has shown that as little as one week of exposure to a high fat, high sugar diet leads to impairments in place but not object recognition memory in the rat. Excess sugar alone had similar effects, and the detrimental effects of diet consumption was linked to increased inflammatory markers in the hippocampus, a critical region involved in memory. Furthermore, obesity-related inflammatory changes have also been described in the human brain that may lead to memory impairments. These memory deficits may contribute to pathological eating behaviour through changes in the amount consumed and timing of eating. The aim of this eBook is to present up-to-date information about the impact of diet and diet-induced obesity on reward driven learning, memory and cognition, encompassing both animal and human literature, and also potential therapeutic targets to attenuate such deficits.

Keywords

Diet --- Obesity --- Memory --- Cognition --- Famine --- Fat --- Sugar --- Behavior --- Neurodevelopment

Regulatory RNAs in the Nervous System, 2nd Edition

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889456574 Year: Pages: 346 DOI: 10.3389/978-2-88945-657-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:43
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Until about a decade ago, the non-coding part of the genome was considered without function. RNA sequencing studies have shown, however, that a considerable part of the non-coding genome is transcribed and that these non-coding RNAs (nc-RNAs) can regulate gene expression. Almost on weekly basis, new findings reveal the regulatory role of nc-RNAs exert in many biological processes. Overall, these studies are making increasingly clear that, both in model organisms and in humans, complexity is not a function of the number of protein-coding genes, but results from the possibility of using combinations of genetic programs and controlling their spatial and temporal regulation during development, senescence and in disease by regulatory RNAs. This has generated a novel picture of gene regulatory networks where regulatory nc-RNAs represent novel layers of regulation. Particularly well-characterized is the role of microRNAs (miRNAs), small nc-RNAs, that bind to mRNAs and regulate gene expression after transcritpion. This message is particularly clear in the nervous system, where miRNAs have been involved in regulating cellular pathways controlling fundamental functions during development, synaptic plasticity and in neurodegenerative disease. It has also been shown that neuronal miRNAs are tightly regulated by electrical activity at the level of transcription, biogenesis, stability and specifically targeted to dendrites and synapses. Deregulation of expression of miRNAs is proposed not only as potential disease biomarker, but it has been implicated directly in the pathogenesis of complex neurodegenerative disease. This so-called RNA revolution also lead to the exploitation of RNA interference and the development of related tools as potential treatment of a vast array of CNS disease that could benefit from regulation of disease-associated genes. In spite of these advancements, the relatively young age of this field together with the inherent high molecular complexity of RNA regulation of biological processes have somewhat hindered its communication to the whole of the neuroscience community. This Research Topic aims at improving this aspect by putting around the same virtual table scientists covering aspects ranging from basic molecular mechanisms of regulatory RNAs in the nervous system to the analysis of the role of specific regulatory RNAs in neurobiological processes of development, plasticity and aging. Furthermore, we included papers analyzing the role of regulatory RNAs in disease models from neuromuscular to higher cognitive functions, and more technically oriented papers dealing with new methodologies to study regulatory RNA biology and its translational potential.

Neuroplasticity and Extracellular Proteolysis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198511 Year: Pages: 151 DOI: 10.3389/978-2-88919-851-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Neuroplasticity refers to the ability of the Central Nervous System (CNS) to alter its structure and function in response to a variety of physiological and pathological processes such as development, cognition, injury or neurological diseases. Since more than four decades, studies on synaptic plasticity in the context of memory and learning attracted a remarkable interest. Soon after first seminal works on synaptic plasticity were published, research in this field was extended by studies on non-synaptic as wells as structural plasticity towards a goal to understand cellular and molecular determinants of cognition. Over the past two decades, yet two additional crucial players in neuroplastic phenomena started to be intensely investigated – glial cells and the extracellular matrix (ECM). Growing awareness that glial cells, especially astrocytes, are important regulators of synaptic functions gave rise to a novel concept of a tri-partite synapse. Also, over the last two decades, a growing body of evidence has accumulated that the extracellular matrix (ECM) in the brain is strongly involved in regulation of neurons, in particular, in synaptic plasticity. Thus, a concept of tetra-partite synapse was put forward by some neuroscientists. The cross-talk between neuron-glia-ECM system involves enzymatic degradation of proteins or peptides and amino acids occurring in each of these brain constituents by means of a variety of proteases. Importantly, it has been realized that proteases such as serine proteases and matrix metalloproteinases, not only accompany “robust” phenomena such as cell division, or development or neurodegnerative conditions but may play a very subtle signaling functions, particularly important in memory acquisition. Indeed, the repertoire of substrates for these enzymes covers a wide variety of proteins known to play important role in the neuroplastic phenomena (e.g. BDNF, TNF-a, ephrin systems, various cell adhesion molecules, etc.). In result, the role of metalloproteinases and such serine proteases as tissue plasminogen activator (tPA), neuropsin or neurotrypsin in synaptic plasticity as well as in learning and memory has been particularly well demonstrated. It needs to be emphasized, however, that in spite of a remarkable progress in this field, several basic questions regarding molecular and cellular mechanisms remain unanswered. Potential involvement of so many important players (various proteases and their substrates in neurons, glia and in ECM) points to an enormous potential for plasticity phenomena but makes also studies into underlying mechanisms particularly difficult. In the proposed Research Topic we provide both review of the current state of the art and present some original reports on specific aspects of the role of proteolysis in neuroplasticity phenomena. The present ebook starts with extensive reviews describing involvement of proteolysis not only in synaptic plasticity but also in regulating endogenous excitability and structural changes at the network, cellular and subcellular levels. Cross-talk between neuroplasticity and proteolysis is also emphasized in the context of development and in relation to various pathologies. Whereas in the first part of the present ebook, the major focus is on metalloproteinases, the successive articles address the role of neuropsin and thrombin. The Research Topic is concluded with a series of articles describing the components of extracellular matrix and adhesion proteins and their elaboration by mechanisms dependent directly or indirectly on proteolysis. We do hope that the present ebook will further stimulate the interest in the fascinating investigations into neuroplasticity-proteolysis cross-talk.

Autism Spectrum Disorders: From genotypes to phenotypes

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196807 Year: Pages: 93 DOI: 10.3389/978-2-88919-680-7 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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This Research Topic covers the pathogenetic processes in Autism Spectrum Disorder (ASD) that underpin the translation of genetic vulnerability to clinically significant symptoms. Available research data in ASD suggests that it is a neural connectivity disorder and that the social communication and related neurobehavioural symptoms result from reduced synchronization between key "social brain" regions. These interconnected neural systems can be understood through the relationship between functionally relevant anatomic areas and neurochemical pathways, the programming of which are genetically modulated during neurodevelopment and mediated through a range of epigenetic and environmental modulators. Elucidating the underlying molecular mechanisms can provide an invaluable window for understanding the neural wiring that regulates higher brain functions and consequent clinical phenotypes. In keeping with the multi modal and diverse origins of ASD, this Research Topic explores the genetic underpinnings and environmental modulation in the aetiology; neural substrates, biomarkers and endophenotypes that underlie clinical characteristics; as well as neurochemical pathways and pathophysiological mechanisms that pave the way for therapeutic interventions. Furthermore, since genetically mediated deficits and consequent functional impairments involve activity-dependent synapse development that depends on postnatal learning and experience, the trajectory towards the final clinical expression could be modulated by early interventions that exploit the neuronal maturation and brain plasticity. However, identifying these diverse pathogenetic processes and tailoring interventions would require subtyping ASD into homogeneous subgroups. In this regard, this topic covers the current state of evidence in the literature through topic reviews as well as ongoing original work that provides tangible hypotheses and directions for future research.

Advances in Neuroimmunology

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ISBN: 9783038425700 9783038425717 Year: Pages: X, 150 DOI: 10.3390/books978-3-03842-571-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2017-12-06 12:41:40
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Neuroimmunity is a relative new and rapidly expanding area of interest that critically impacts normal brain function and a wide range of neurological disorders. Neuroimmune mechanisms operate within the nervous system and between the nervous system and periphery. Glial cells of the nervous system play a primary role in neuroimmunity, through their ability to produce and respond to neuroimmune signaling factors, which serve a number of functions, such as homeostatic regulation of nervous system function and defense against insult and infection. Dysfunction of the neuroimmune system is now thought to be an important contributing factor to many disease and injury states.The purpose of this Special Issue is to provide a representative view of current research in this growing field, with an emphasis on the central nervous system.

DHA for Optimal Health

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ISBN: 9783038429715 9783038429722 Year: Pages: X, 276 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Psychology
Added to DOAB on : 2018-06-26 16:08:39
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This Special Issue of Nutrients, entitled "DHA for Optimal Health", consists of evidence-based original research or reviews of the scientific literature. Manuscripts focus on the evidence that underpins dietary requirements throughout the lifespan (from in-utero to the elderly) for optimal brain function and/or prevention (or treatment) of disease.

Deciphering serotonin's role in neurodevelopment

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192762 Year: Pages: 131 DOI: 10.3389/978-2-88919-276-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-03 13:02:24
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One of the most challenging questions in neurobiology to tackle is how the serotonergic system steers neurodevelopment. With the increase in serotonergic anxiolytic and antidepressant drugs, serotonin was thought to signal adversity or to serve as an emotional signal. However, a vast amount of literature is accumulating showing that serotonin rather mediates neuroplasticity and plays a key role in early developmental processes. For instance, selective serotonin reuptake inhibitors (SSRIs), serving as antidepressants, increase neurogenesis and trigger autism-related brain and behavioural changes during embryonic and perinatal exposure. Moreover, serotonin transporter gene variation is associated with alterations in corticolimbic neuroplasticity, autism-related neuroanatomical changes, as well alterations in social behaviour. Hence, the view is emerging that early life changes in serotonin levels influence the developmental course of socio-emotional brain circuits that are relevant for autism and other neurodevelopmental disorders. It is particularly exciting that the effects of embryonic and perinatal SSRI exposure and serotonin transporter gene variation on neurodevelopment seem to overlap to a large extent, at the cellular as well as the behavioural level. Yet, the precise mechanisms by which serotonin mediates neurodevelopment in the normal and ´autistic´ brain is unclear. Whereas serotonin has a placental origin during early gestation, serotonergic neurons develop during midgestation under the control of a cascade of transcription factors determining the fate of mid-hindbrain neurons that together for the Raphe nuclei. These neurons are among the earliest neurons to be generated, and because serotonin is released before any conventional synapses are formed, serotonin is suspected to influence crucial neurodevelopmental processes such as proliferation,migration and network formation. During late gestation they target their final destinations in, for instance, the cortex, where they affect the secretion of reelin. Reelin is a secreted extracellular matrix glycoprotein that helps to regulate processes of neuronal migration and positioning in the developing cortex by controlling cell–cell interactions. During the late prenatal and early postnatal phase (in rodents) serotonin further shapes the outgrowth of projecting neurons, synaptic connectivity, and the morphology of white fiber tracts. This is under the influence of transient serotonin transporter expression in (thalamo)cortical projections, sensory and prefrontal cortices and the hippocampus, as well as the local expression patterns of 5-HT1A, 5-HT1B and 5-HT3A receptors that each exert their specific roles in neuronal migration, remodeling of axons, and controlling dendritic complexity. There is also evidence that serotonin influences neural activity in locus ceroeleus neurons. Hence, serotonin appears to influence the development of both short- and long-distance connections in the brain. This Research Topic is devoted to studies pinpointing the neurodevelopmental effects of serotonin in relation to prenatal SSRI exposure, serotonin transporter gene variation, and autism/neurodevelopmental disorders, using a wide-variety of cellular and molecular neurobiological techniques like, (epi)genetics, knockout, knockdown, neuroanatomy, physiology, MRI and behaviour in rodents and humans. We especially encouraged attempts to cross-link the neurodevelopmental processes across the fields of prenatal SSRI exposure, serotonin transporter gene variation, and autism/neurodevelopmental disorders, as well as new views on the positive or beneficial effects on serotonin-mediated neurodevelopmental changes.

Bridging the gap before and after birth: Methods and technologies to explore the functional neural development in humans

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196876 Year: Pages: 114 DOI: 10.3389/978-2-88919-687-6 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Infant brain damage is a serious condition that affects millions of babies each year. The period from late gestation to the first year of life is the most critical one for the development of central and autonomous nervous systems. Medical conditions such as preterm birth may compromise brain function and the end result usually is that the baby may experience long-term neurological problems related to a wide range of psychological, physical and functional complications, with consequent life-long burdens for the individuals and their families, and a high socio-economic impact for the health care system and the whole of society. During the last years, several techniques have been employed to monitor the brain functional development in utero and after birth. As well, various analytical methods have been used to understand the functional maturation of the brain and the autonomous nervous system. However, in spite of the rapid improvement of diagnostic methods and procedures, there is still a widely recognized, severe shortage of clinically viable means for the high quality monitoring of the brain function in early life with a direct relevance to acute neurological illness and future neurocognitive outcomes. The studies collected in this e-book document the most recent advancements in monitoring systems, analytical methods and clinical diagnostic procedures that contribute to increase our knowledge of the functional development of the human brain and autonomous nervous system during pregnancy and after birth, with the ultimate goal of reducing fetal impairment and improving healthcare in the neonatal and infant period.

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