scholarly journals Neurogenetic and Neuroepigenetic Mechanisms in Cognitive Health and Disease

2020 ◽  
Vol 13 ◽  
Author(s):  
Davide Martino Coda ◽  
Johannes Gräff
Keyword(s):  
Cognitive Processes ◽  
Molecular Mechanisms ◽  
Disease Risk ◽  
Phenotypic Variability ◽  
Complete Understanding ◽  
Brain Functioning ◽  
Brain Functions ◽  
Neuronal Processes ◽  
Health And Disease ◽  
The Brain

Over the last two decades, the explosion of experimental, computational, and high-throughput technologies has led to critical insights into how the brain functions in health and disease. It has become increasingly clear that the vast majority of brain activities result from the complex entanglement of genetic factors, epigenetic changes, and environmental stimuli, which, when altered, can lead to neurodegenerative and neuropsychiatric disorders. Nevertheless, a complete understanding of the molecular mechanisms underlying neuronal activities and higher-order cognitive processes continues to elude neuroscientists. Here, we provide a concise overview of how the interaction between the environment and genetic as well as epigenetic mechanisms shapes complex neuronal processes such as learning, memory, and synaptic plasticity. We then consider how this interaction contributes to the development of neurodegenerative and psychiatric disorders, and how it can be modeled to predict phenotypic variability and disease risk. Finally, we outline new frontiers in neurogenetic and neuroepigenetic research and highlight the challenges these fields will face in their quest to decipher the molecular mechanisms governing brain functioning.

scholarly journals Sublethal Exposure Effects of the Neonicotinoid Clothianidin Strongly Modify the Brain Transcriptome and Proteome in the Male Moth Agrotis ipsilon

Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 152
Author(s):  
Camille Meslin ◽  
Françoise Bozzolan ◽  
Virginie Braman ◽  
Solenne Chardonnet ◽  
Cédric Pionneau ◽  
...  
Keyword(s):  
Sex Pheromone ◽  
Molecular Mechanisms ◽  
Insect Pest ◽  
Agrotis Ipsilon ◽  
Positive Effects ◽  
Male Moth ◽  
Hormetic Effect ◽  
Pest Insects ◽  
Neuronal Processes ◽  
The Brain

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids such as clothianidin. The residual accumulation of low concentrations of these insecticides can have positive effects on target pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction and olfactory synaptic transmission is cholinergic, neonicotinoid residues could indeed modify chemical communication. We recently showed that treatments with low doses of clothianidin could induce hormetic effects on behavioral and neuronal sex pheromone responses in the male moth, Agrotis ipsilon. In this study, we used high-throughput RNAseq and proteomic analyses from brains of A. ipsilon males that were intoxicated with a low dose of clothianidin to investigate the molecular mechanisms leading to the observed hormetic effect. Our results showed that clothianidin induced significant changes in transcript levels and protein quantity in the brain of treated moths: 1229 genes and 49 proteins were differentially expressed upon clothianidin exposure. In particular, our analyses highlighted a regulation in numerous enzymes as a possible detoxification response to the insecticide and also numerous changes in neuronal processes, which could act as a form of acclimatization to the insecticide-contaminated environment, both leading to enhanced neuronal and behavioral responses to sex pheromone.

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

scholarly journals The restless brain: how intrinsic activity organizes brain function

2015 ◽  
Vol 370 (1668) ◽  
pp. 20140172 ◽  
Author(s):  
Marcus E. Raichle
Keyword(s):  
Brain Function ◽  
Functional Organization ◽  
Sensory Information ◽  
Intrinsic Activity ◽  
Systems Neuroscience ◽  
Brain Functions ◽  
Molecular Neuroscience ◽  
Constant State ◽  
Health And Disease ◽  
The Brain

Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease.

scholarly journals Bursting at the Seams: Molecular Mechanisms Mediating Astrocyte Swelling

2019 ◽  
Vol 20 (2) ◽  
pp. 330 ◽  
Author(s):  
Audrey Lafrenaye ◽  
J. Simard
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Predictors Of Outcome ◽  
Cell Type ◽  
Brain Swelling ◽  
Astrocyte Swelling ◽  
Health And Disease ◽  
The One ◽  
The Brain ◽  
Cellular Swelling

Brain swelling is one of the most robust predictors of outcome following brain injury, including ischemic, traumatic, hemorrhagic, metabolic or other injury. Depending on the specific type of insult, brain swelling can arise from the combined space-occupying effects of extravasated blood, extracellular edema fluid, cellular swelling, vascular engorgement and hydrocephalus. Of these, arguably the least well appreciated is cellular swelling. Here, we explore current knowledge regarding swelling of astrocytes, the most abundant cell type in the brain, and the one most likely to contribute to pathological brain swelling. We review the major molecular mechanisms identified to date that contribute to or mitigate astrocyte swelling via ion transport, and we touch upon the implications of astrocyte swelling in health and disease.

CURRENT AND TRADITIONAL VIEWS ON THE BRAIN WORKS

2018 ◽  
Vol 16 (2) ◽  
pp. 201-212
Author(s):  
Bożydar L.J. Kaczmarek ◽  
Katarzyna Markiewicz
Keyword(s):  
Brain Imaging ◽  
Imaging Techniques ◽  
Brain Disorders ◽  
New Techniques ◽  
Brain Functioning ◽  
Brain Functions ◽  
New Methods ◽  
New Ideas ◽  
Theoretical Considerations ◽  
The Brain

The present paper argues that the development of a new methodology in studying the brain has resulted in a change of our views on the way it works, has seen the emergence of new ideas, and a considerable modification of traditionally accepted theories. The most significant are neuroplasticity, negative activity network (NAT), the nature of aphasic disorders, and the approach to the localization of brain functions. New brain imaging techniques have confirmed also the ability to change the neuronal circuits by mental force. Moreover, new techniques have brought about a rise in new methods for both the diagnosis and rehabilitation of individuals with various brain disorders. Most valuable in this respect has proved to be neurofeedback. We have concentrated on the most important contributions of Prof. Pąchalska in the implementation and development of these new ideas on brain functioning. We also emphasize the fact that her theoretical considerations are firmly based upon her extensive (forty years) work with brain damaged patients.

scholarly journals Neuroprotective effects of physical exercise: Implications in health and disease

2021 ◽  
Vol 68 (3) ◽  
pp. 383-389
Author(s):  
Sebastian Romeo Pintilie ◽  
◽  
Alice D. Condrat ◽  
Adriana Fodor ◽  
Adela-Viviana Sitar-Tăut ◽  
...  
Keyword(s):  
Physical Activity ◽  
Physical Exercise ◽  
Molecular Mechanisms ◽  
Cellular Level ◽  
Neuroprotective Effects ◽  
Chemical Effects ◽  
Physical Exercises ◽  
Health And Disease ◽  
Molecular Aspects ◽  
The Brain

Physical exercises have long been linked to numerous health improvements, ranging from cardiovascular to psychiatric. In this review, we take a closer look on its anatomical, physiological and chemical effects on the brain. Starting from the clinical to the cellular level, we will analyze the neurogenesis, anti-inflammatory effects on Brain-Blood Barrier and synaptic plasticity, outlining known molecular aspects that are influenced by physical activity, such as: gene expression, changes of growth factors and neurotransmitter levels and means of reverting molecular mechanisms of ageing. The brain derived neurotrophic factor (BDNF) is one of the central molecules that links the physical exercise to neurogenesis, neuroprotection, cognitive functions, dendritic growth, memory formation and many more. We indicate the correlation between physical activity and mental health in diseases like depression, Alzheimer’s dementia and Parkinson’s disease.

scholarly journals Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders

2019 ◽  
Vol 20 (4) ◽  
pp. 996 ◽  
Author(s):  
Eiji Shigetomi ◽  
Kozo Saito ◽  
Fumikazu Sano ◽  
Schuichi Koizumi
Keyword(s):  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Brain Disease ◽  
Reactive Astrocytes ◽  
Brain Functions ◽  
Progression Of Disease ◽  
Brain Insults ◽  
The Brain

Astrocytes are abundant cells in the brain that regulate multiple aspects of neural tissue homeostasis by providing structural and metabolic support to neurons, maintaining synaptic environments and regulating blood flow. Recent evidence indicates that astrocytes also actively participate in brain functions and play a key role in brain disease by responding to neuronal activities and brain insults. Astrocytes become reactive in response to injury and inflammation, which is typically described as hypertrophy with increased expression of glial fibrillary acidic protein (GFAP). Reactive astrocytes are frequently found in many neurological disorders and are a hallmark of brain disease. Furthermore, reactive astrocytes may drive the initiation and progression of disease processes. Recent improvements in the methods to visualize the activity of reactive astrocytes in situ and in vivo have helped elucidate their functions. Ca2+ signals in reactive astrocytes are closely related to multiple aspects of disease and can be a good indicator of disease severity/state. In this review, we summarize recent findings concerning reactive astrocyte Ca2+ signals. We discuss the molecular mechanisms underlying aberrant Ca2+ signals in reactive astrocytes and the functional significance of aberrant Ca2+ signals in neurological disorders.

scholarly journals What cell biologists should know about the National Institutes of Health BRAIN Initiative

2015 ◽  
Vol 26 (25) ◽  
pp. 4539-4540
Author(s):  
Thomas R. Insel ◽  
Walter Koroshetz
Keyword(s):  
Brain Research ◽  
National Institutes Of Health ◽  
Next Generation ◽  
Brain Functions ◽  
Leading Role ◽  
Cell Diversity ◽  
Health And Disease ◽  
Circuit Function ◽  
The Brain

The BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is an ambitious project to develop innovative tools for a deeper understanding of how the brain functions in health and disease. Early programs in the National Institutes of Health BRAIN Initiative focus on tools for next-generation imaging and recording, studies of cell diversity and cell census, and integrative approaches to circuit function. In all of these efforts, cell biologists can play a leading role.

scholarly journals Synapse formation: from cellular and molecular mechanisms to neurodevelopmental and neurodegenerative disorders

2019 ◽  
Vol 121 (4) ◽  
pp. 1381-1397 ◽  
Author(s):  
Shadab Batool ◽  
Hussain Raza ◽  
Jawwad Zaidi ◽  
Saba Riaz ◽  
Sean Hasan ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Brain Functions ◽  
Mature Brain ◽  
Behavioral Needs ◽  
Neuronal Assembly ◽  
The Brain ◽  
Shed Light

The precise patterns of neuronal assembly during development determine all functional outputs of a nervous system; these may range from simple reflexes to learning, memory, cognition, etc. To understand how brain functions and how best to repair it after injury, disease, or trauma, it is imperative that we first seek to define fundamental steps mediating this neuronal assembly. To acquire the sophisticated ensemble of highly specialized networks seen in a mature brain, all proliferated and migrated neurons must extend their axonal and dendritic processes toward targets, which are often located at some distance. Upon contact with potential partners, neurons must undergo dramatic structural changes to become either a pre- or a postsynaptic neuron. This connectivity is cemented through specialized structures termed synapses. Both structurally and functionally, the newly formed synapses are, however, not static as they undergo consistent changes in order for an animal to meet its behavioral needs in a changing environment. These changes may be either in the form of new synapses or an enhancement of their synaptic efficacy, referred to as synaptic plasticity. Thus, synapse formation is not restricted to neurodevelopment; it is a process that remains active throughout life. As the brain ages, either the lack of neuronal activity or cell death render synapses dysfunctional, thus giving rise to neurodegenerative disorders. This review seeks to highlight salient steps that are involved in a neuron’s journey, starting with the establishment, maturation, and consolidation of synapses; we particularly focus on identifying key players involved in the synaptogenic program. We hope that this endeavor will not only help the beginners in this field to understand how brain networks are assembled in the first place but also shed light on various neurodevelopmental, neurological, neurodegenerative, and neuropsychiatric disorders that involve synaptic inactivity or dysfunction.

scholarly journals The Physiological Action of Picolinic Acid in the Human Brain

2009 ◽  
Vol 2 ◽  
pp. IJTR.S2469 ◽  
Author(s):  
R.S. Grant ◽  
S.E. Coggan ◽  
G.A. Smythe
Keyword(s):  
Human Brain ◽  
Physiological Function ◽  
Current Knowledge ◽  
Picolinic Acid ◽  
Kynurenine Pathway ◽  
The Body ◽  
Complete Understanding ◽  
Wide Range ◽  
Health And Disease ◽  
The Brain

Picolinic Acid is an endogenous metabolite of L-tryptophan (TRP) that has been reported to possess a wide range of neuroprotective, immunological, and anti-proliferative affects within the body. However the salient physiological function of this molecule is yet to be established. The synthesis of picolinic acid as a product of the kynurenine pathway (KP) suggests that, similar to other KP metabolites, picolinic acid may play a role in the pathogenesis of inflammatory disorders within the CNS and possibly other organs. In this paper we review the limited body of literature dealing with the physiological actions of picolinic acid in the CNS and its associated synthesis via the kynurenine pathway in health and disease. Discrepancies and gaps in our current knowledge of picolinic acid are identified highlighting areas of research to promote a more complete understanding of its endogenous function in the brain.

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