Brain Fuel Utilization in the Developing Brain

2019 ◽  
Vol 75 (1) ◽  
pp. 8-18 ◽  
Author(s):  
Pascal Steiner
Keyword(s):  
Brain Development ◽  
Ketone Bodies ◽  
Brain Connectivity ◽  
Signal Transmission ◽  
Neuronal Cell ◽  
Building Blocks ◽  
The Body ◽  
Adult Brain ◽  
Acid Oxidation ◽  
The Brain

During pregnancy and infancy, the human brain is growing extremely fast; the brain volume increases significantly, reaching 36, 72, and 83% of the volume of adults at 2–4 weeks, 1 year, and 2 years of age, respectively, which is essential to establish the neuronal networks and capacity for the development of cognitive, motor, social, and emotional skills that will be continually refined throughout childhood and adulthood. Such dramatic changes in brain structure and function are associated with very large energetic demands exceeding by far those of other organs of the body. It has been estimated that during childhood the brain may account for up to 60% of the body basal energetic requirements. While the main source of energy for the adult brain is glucose, it appears that it is not sufficient to sustain the dramatic metabolic demands of the brain during its development. Recently, it has been proposed that this energetic challenge is solved by the ability of the brain to use ketone bodies (KBs), produced from fatty acid oxidation, as a complement source of energy. Here, we first describe the main cellular and physiological processes that drive brain development along time and how different brain metabolic pathways are engaged to support them. It has been assumed that the majority of energetic substrates are used to support neuronal activity and signal transmission. We discuss how glucose and KBs are metabolized to provide the carbon backbones used to synthesize lipids, nucleic acid, and cholesterol, which are indispensable building blocks of neuronal cell proliferation and are also used to establish and refine brain connectivity through synapse formation/elimination and myelination. We conclude that glucose and KBs are not only important to support the energy needs of the brain under development, but they are also essential substrates for the biosynthesis of macromolecules underlying structural brain growth and reorganization. We emphasize that glucose and fatty acids supporting the production of KBs are provided in complex food matrices, such as breast milk, and understanding how their availability impacts the brain will be key to promote adequate nutrition to support brain metabolism and, therefore, optimal brain development.

scholarly journals Determination of Dynamic Brain Connectivity via Spectral Analysis

2021 ◽  
Vol 15 ◽  
Author(s):  
Peter A. Robinson ◽  
James A. Henderson ◽  
Natasha C. Gabay ◽  
Kevin M. Aquino ◽  
Tara Babaie-Janvier ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
Brain Structure ◽  
Brain Connectivity ◽  
Spatial Scales ◽  
Effective Connectivity ◽  
Physical Nature ◽  
Building Blocks ◽  
Brain Dynamics ◽  
Compact Representation ◽  
The Brain

Spectral analysis based on neural field theory is used to analyze dynamic connectivity via methods based on the physical eigenmodes that are the building blocks of brain dynamics. These approaches integrate over space instead of averaging over time and thereby greatly reduce or remove the temporal averaging effects, windowing artifacts, and noise at fine spatial scales that have bedeviled the analysis of dynamical functional connectivity (FC). The dependences of FC on dynamics at various timescales, and on windowing, are clarified and the results are demonstrated on simple test cases, demonstrating how modes provide directly interpretable insights that can be related to brain structure and function. It is shown that FC is dynamic even when the brain structure and effective connectivity are fixed, and that the observed patterns of FC are dominated by relatively few eigenmodes. Common artifacts introduced by statistical analyses that do not incorporate the physical nature of the brain are discussed and it is shown that these are avoided by spectral analysis using eigenmodes. Unlike most published artificially discretized “resting state networks” and other statistically-derived patterns, eigenmodes overlap, with every mode extending across the whole brain and every region participating in every mode—just like the vibrations that give rise to notes of a musical instrument. Despite this, modes are independent and do not interact in the linear limit. It is argued that for many purposes the intrinsic limitations of covariance-based FC instead favor the alternative of tracking eigenmode coefficients vs. time, which provide a compact representation that is directly related to biophysical brain dynamics.

scholarly journals The diacylglycerol lipases: structure, regulation and roles in and beyond endocannabinoid signalling

2012 ◽  
Vol 367 (1607) ◽  
pp. 3264-3275 ◽  
Author(s):  
Melina Reisenberg ◽  
Praveen K. Singh ◽  
Gareth Williams ◽  
Patrick Doherty
Keyword(s):  
Dopaminergic Neurons ◽  
Cannabinoid Receptors ◽  
Homology Modelling ◽  
Detailed Examination ◽  
The Body ◽  
Adult Brain ◽  
And Migration ◽  
Regulatory Loop ◽  
Translational Mechanisms ◽  
The Brain

The diacylglycerol lipases (DAGLs) hydrolyse diacylglycerol to generate 2-arachidonoylglycerol (2-AG), the most abundant ligand for the CB 1 and CB 2 cannabinoid receptors in the body. DAGL-dependent endocannabinoid signalling regulates axonal growth and guidance during development, and is required for the generation and migration of new neurons in the adult brain. At developed synapses, 2-AG released from postsynaptic terminals acts back on presynaptic CB 1 receptors to inhibit the secretion of both excitatory and inhibitory neurotransmitters, with this DAGL-dependent synaptic plasticity operating throughout the nervous system. Importantly, the DAGLs have functions that do not involve cannabinoid receptors. For example, 2-AG is the precursor of arachidonic acid in a pathway that maintains the level of this essential lipid in the brain and other organs. This pathway also drives the cyclooxygenase-dependent generation of inflammatory prostaglandins in the brain, which has recently been implicated in the degeneration of dopaminergic neurons in Parkinson's disease. Remarkably, we still know very little about the mechanisms that regulate DAGL activity—however, key insights can be gleaned by homology modelling against other α/β hydrolases and from a detailed examination of published proteomic studies and other databases. These identify a regulatory loop with a highly conserved signature motif, as well as phosphorylation and palmitoylation as post-translational mechanisms likely to regulate function.

scholarly journals Vitamin C In Neuropsychiatry

2015 ◽  
Vol 16 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Dragan M. Pavlović ◽  
Merdin Š. Markišić ◽  
Aleksandra M. Pavlović
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
The Body ◽  
Adult Brain ◽  
Normal Brain ◽  
Positive Effects ◽  
Normal Brain Function ◽  
High Concentrations ◽  
High Doses ◽  
The Brain

Abstract Vitamins are necessary factors in human development and normal brain function. Vitamin C is a hydrosoluble compound that humans cannot produce; therefore, we are completely dependent on food intake for vitamin C. Ascorbic acid is an important antioxidative agent and is present in high concentrations in neurons and is also crucial for collagen synthesis throughout the body. Ascorbic acid has a role in modulating many essential neurotransmitters, enables neurogenesis in adult brain and protects cells against infection. While SVCT1 enables the absorption of vitamin C in the intestine, SVCT2 is primarily located in the brain. Ascorbate deficiency is classically expressed as scurvy, which is lethal if not treated. However, subclinical deficiencies are probably much more frequent. Potential fields of vitamin C therapy are in neurodegenerative, cerebrovascular and affective diseases, cancer, brain trauma and others. For example, there is some data on its positive effects in Alzheimer’s disease. Various dosing regimes are used, but ascorbate is safe, even in high doses for protracted periods. Better designed studies are needed to elucidate all of the potential therapeutic roles of vitamin C.

scholarly journals Anatomical Differences between Children and Adults

2020 ◽  
Vol 8 (05) ◽  
pp. 355-359
Author(s):  
Rengin Kosif ◽  
Rabia Keçialan
Keyword(s):  
Subcutaneous Tissue ◽  
Vastus Lateralis ◽  
Rectus Femoris ◽  
The Body ◽  
Adult Brain ◽  
Skeletal Structure ◽  
School Age ◽  
Pediatric Drug ◽  
Gynecological Examination ◽  
The Brain

In this review,   anatomical differences between  child   and   adult   were   mentioned.   These differences are especially apparent in infancy and preschool term. When the child reaches the school age term, the differences begin to decrease gradually.  When the child reaches the age of 18, the child has the same characteristics as the adult. The main differences include skin, subcutaneous tissue, total amount of water in the body, muscles preferred in pharmaceutical applications,   external   ear   structure,   Eustachian   tube,   anatomy   of   the   eye,   bone   skeletal structure, spinal cord and brain, respiratory tract, digestive organs, cardiovascular system and urinary system. The differences especially between child and adult brain structure are striking. The brain tissue in the child is more sensitive, calvarium is thinner, subarachnoid space is narrower.   Morover;   the   differences   in   gynecological   examination   and   lumber   puncture practices   were   also   reviewed.  In   adults,   gluteal   muscles   are   used   in   intramuscular applications, while in infants, rectus femoris and vastus lateralis muscles are commonly used. These anatomical differences are important for the diagnosis and treatment of the doctors. Nurses should take these differences into account in pediatric drug applications in the clinic and in the care of children. Clinicians should know that children are not small adults.

Arithmetic in the Child and Adult Brain

2014 ◽  
Author(s):  
Vinod Menon
Keyword(s):  
Skill Acquisition ◽  
Temporal Cortex ◽  
Occipital Cortex ◽  
Building Blocks ◽  
Memory Systems ◽  
Adult Brain ◽  
Long Term Memory ◽  
Neural Basis ◽  
Mature Adult ◽  
The Brain

This review examines brain and cognitive processes involved in arithmetic. I take a distinctly developmental perspective because neither the cognitive nor the brain processes involved in arithmetic can be adequately understood outside the framework of how developmental processes unfold. I review four basic neurocognitive processes involved in arithmetic, highlighting (1) the role of core dorsal parietal and ventral temporal-occipital cortex systems that form basic building blocks from which number form and quantity representations are constructed in the brain; (2) procedural and working memory systems anchored in the basal ganglia and frontoparietal circuits, which create short-term representations that allow manipulation of multiple discrete quantities over several seconds; (3) episodic and semantic memory systems anchored in the medial and lateral temporal cortex that play an important role in long-term memory formation and generalization beyond individual problem attributes; and (4) prefrontal cortex control processes that guide allocation of attention resources and retrieval of facts from memory in the service of goal-directed problem solving. Next I examine arithmetic in the developing brain, first focusing on studies comparing arithmetic in children and adults, and then on studies examining development in children during critical stages of skill acquisition. I highlight neurodevelopmental models that go beyond parietal cortex regions involved in number processing, and demonstrate that brain systems and circuits in the developing child brain are clearly not the same as those seen in more mature adult brains sculpted by years of learning. The implications of these findings for a more comprehensive view of the neural basis of arithmetic in both children and adults are discussed.

The Brain/MINDS project aimed at establishing the marmoset as a model organism for neurobiology and establishing the genetic and biochemical elements of their neural development

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 86-88
Author(s):  
Tomomi Shimogori
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Molecular Mechanisms ◽  
Mental Disease ◽  
Visual Stimuli ◽  
The Body ◽  
Proper Function ◽  
Newborn Mouse ◽  
Model Animal ◽  
The Brain

The brain is the most sophisticated and intricate organ in the body. Billions of neurons interconnect and form distinct regions which process different neural activities. The development of the brain during pregnancy and early post-natal life is extremely sensitive, complex and crucial to proper function over the life of a person. This is the most plastic time of the brain. It is changing constantly and reacting to the different stimuli encountered by the individual. The lack of a particular stimulus can have a profound effect on the later structure and function of the brain. For example, if a newborn mouse has an eye covered so it receives no light, visual cortex, where normally processes binocular visual stimuli, develops to process visual stimuli only from the open eye. This cannot be altered later on even when both eyes are opened; the mouse remains weak in one eye despite there being nothing wrong with the eye itself. Studying this early time period of brain development presents many problems. Investigation is hampered by the difficulty in accessing and manipulating the brain as well as the huge variety of factors that contribute to brain development. Currently, most work is conducted in rodents, primarily because there are a large range of genetic tools available. This is useful to an extent and has demonstrated key findings that appear to be relevant to most mammalian species. However, the human brain is quite different to the mouse brain. It has adapted to very different tasks required of mice compared to humans and therefore there is a knowledge gap to bridge in this area. In addition to this, examination of global gene expression in the brain has only truly become viable in the last 10 years. The same can also be said of the ability to analyse the development process at a biochemical level. Dr Tomomi Shimogori of the RIKEN Center for Brain Science, Japan, has been tackling these difficulties through her work on the molecular mechanisms of brain development. She has worked on rodents, but is now developing a model in the common marmoset based around the creation of a gene atlas. Working on the primate should help fill in the gap between rodent and human. Shimogori explains why the marmoset was chosen: 'One of the biggest advantages of using marmosets as a model animal is that many of its behaviours share similarities with human behaviours, and thus has potential for use in understanding the underlying mechanisms of human brain function and mental disease

scholarly journals Cerebral Metabolic Adaptation and Ketone Metabolism after Brain Injury

2007 ◽  
Vol 28 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Mayumi L Prins
Keyword(s):  
Brain Injury ◽  
Therapeutic Potential ◽  
Ketone Bodies ◽  
Cerebral Metabolism ◽  
The Body ◽  
Adult Brain ◽  
Metabolic Adaptation ◽  
Alternative Substrate ◽  
Energy Demands ◽  
Age Related

The developing central nervous system has the capacity to metabolize ketone bodies. It was once accepted that on weaning, the ‘post-weaned/adult’ brain was limited solely to glucose metabolism. However, increasing evidence from conditions of inadequate glucose availability or increased energy demands has shown that the adult brain is not static in its fuel options. The objective of this review is to summarize the body of literature specifically regarding cerebral ketone metabolism at different ages, under conditions of starvation and after various pathologic conditions. The evidence presented supports the following findings: (1) there is an inverse relationship between age and the brain's capacity for ketone metabolism that continues well after weaning; (2) neuroprotective potentials of ketone administration have been shown for neurodegenerative conditions, epilepsy, hypoxia/ischemia, and traumatic brain injury; and (3) there is an age-related therapeutic potential for ketone as an alternative substrate. The concept of cerebral metabolic adaptation under various physiologic and pathologic conditions is not new, but it has taken the contribution of numerous studies over many years to break the previously accepted dogma of cerebral metabolism. Our emerging understanding of cerebral metabolism is far more complex than could have been imagined. It is clear that in addition to glucose, other substrates must be considered along with fuel interactions, metabolic challenges, and cerebral maturation.

scholarly journals Down-regulation of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by insulin: the role of the forkhead transcription factor FKHRL1

2002 ◽  
Vol 366 (1) ◽  
pp. 289-297 ◽  
Author(s):  
Alícia NADAL ◽  
Pedro F. MARRERO ◽  
Diego HARO
Keyword(s):  
Ketone Bodies ◽  
Control Site ◽  
Luciferase Reporter ◽  
Acid Oxidation ◽  
Transcription Start ◽  
Forkhead Transcription Factor ◽  
The Brain

Normal physiological responses to carbohydrate shortages cause the liver to increase the production of ketone bodies from the acetyl-CoA generated from fatty acid oxidation. This allows the use of ketone bodies for energy, thereby preserving the limited glucose for use by the brain. This adaptative response is switched off by insulin rapidly inhibiting the expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (HMGCS2) gene, which is a key control site of ketogenesis. We decided to investigate the molecular mechanism of this inhibition. In the present study, we show that FKHRL1, a member of the forkhead in rhabdosarcoma (FKHR) subclass of the Fox family of transcription factors, stimulates transcription from transfected 3-hydroxy-3-methylglutaryl-CoA synthase promoter-luciferase reporter constructs, and that this stimulation is repressed by insulin. An FKHRL1-responsive sequence AAAAATA, located 211bp upstream of the HMGCS2 gene transcription start site, was identified by deletion analysis. It binds FKHRL1 in vivo and in vitro and confers FKHRL1 responsiveness on homologous and heterologous promoters. If it is mutated, it partially blocks the effect of insulin in HepG2 cells, both in the absence and presence of overexpressed FKHRL1. These results suggest that FKHRL1 contributes to the regulation of HMGCS2 gene expression by insulin.

scholarly journals Activation of endogenous retroviruses during brain development causes neuroinflammation

2020 ◽  
Author(s):  
Marie E Jönsson ◽  
Raquel Garza ◽  
Yogita Sharma ◽  
Rebecca Petri ◽  
Erik Södersten ◽  
...  
Keyword(s):  
Brain Development ◽  
Transcriptional Activation ◽  
Neural Progenitor Cells ◽  
Large Fraction ◽  
Endogenous Retroviruses ◽  
Adult Brain ◽  
Potential Trigger ◽  
Mammalian Genomes ◽  
The Brain

AbstractEndogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for neuroinflammation, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERV expression in excitatory neurons in the adult brain. Neuronal ERV expression was linked to inflammation, including activated microglia, and aggregates of ERV-derived proteins. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in neuroinflammation.

scholarly journals Functional analysis of enhancer elements regulating the expression of the Drosophila homeodomain transcription factor DRx by gene targeting

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Christine Klöppel ◽  
Kirsten Hildebrandt ◽  
Dieter Kolb ◽  
Nora Fürst ◽  
Isabelle Bley ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Brain Development ◽  
Gene Targeting ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Adult Brain ◽  
Central Complex ◽  
Larval Brain ◽  
Endogenous Expression ◽  
The Brain

Abstract Background The Drosophila brain is an ideal model system to study stem cells, here called neuroblasts, and the generation of neural lineages. Many transcriptional activators are involved in formation of the brain during the development of Drosophila melanogaster. The transcription factor Drosophila Retinal homeobox (DRx), a member of the 57B homeobox gene cluster, is also one of these factors for brain development. Results In this study a detailed expression analysis of DRx in different developmental stages was conducted. We show that DRx is expressed in the embryonic brain in the protocerebrum, in the larval brain in the DM and DL lineages, the medulla and the lobula complex and in the central complex of the adult brain. We generated a DRx enhancer trap strain by gene targeting and reintegration of Gal4, which mimics the endogenous expression of DRx. With the help of eight existing enhancer-Gal4 strains and one made by our group, we mapped various enhancers necessary for the expression of DRx during all stages of brain development from the embryo to the adult. We made an analysis of some larger enhancer regions by gene targeting. Deletion of three of these enhancers showing the most prominent expression patterns in the brain resulted in specific temporal and spatial loss of DRx expression in defined brain structures. Conclusion Our data show that DRx is expressed in specific neuroblasts and defined neural lineages and suggest that DRx is another important factor for Drosophila brain development.

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