scholarly journals The Expression and Distributions of ANP32A in the Developing Brain

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shanshan Wang ◽  
Yunliang Wang ◽  
Qingshan Lu ◽  
Xinshan Liu ◽  
Fuyu Wang ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Fetal Brain ◽  
Tissue Expression ◽  
Developing Brain ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Dependent Manner ◽  
Growing Up ◽  
Embryonic Mouse ◽  
And Function

Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A (ANP32A), has multiple functions involved in neuritogenesis, transcriptional regulation, and apoptosis. However, whether ANP32A has an effect on the mammalian developing brain is still in question. In this study, it was shown that brain was the organ that expressed the most abundant ANP32A by human multiple tissue expression (MTE) array. The distribution of ANP32A in the different adult brain areas was diverse dramatically, with high expression in cerebellum, temporal lobe, and cerebral cortex and with low expression in pons, medulla oblongata, and spinal cord. The expression of ANP32A was higher in the adult brain than in the fetal brain of not only humans but also mice in a time-dependent manner. ANP32A signals were dispersed accordantly in embryonic mouse brain. However, ANP32A was abundant in the granular layer of the cerebellum and the cerebral cortex when the mice were growing up, as well as in the Purkinje cells of the cerebellum. The variation of expression levels and distribution of ANP32A in the developing brain would imply that ANP32A may play an important role in mammalian brain development, especially in the differentiation and function of neurons in the cerebellum and the cerebral cortex.

scholarly journals Mechanisms of L-Triiodothyronine-Induced Inhibition of Synaptosomal Na+-K+-ATPase Activity in Young Adult Rat Brain Cerebral Cortex

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Pradip K. Sarkar ◽  
Avijit Biswas ◽  
Arun K. Ray ◽  
Joseph V. Martin
Keyword(s):  
Cerebral Cortex ◽  
Atpase Activity ◽  
Adrenergic Receptor ◽  
Receptor Activation ◽  
Mammalian Brain ◽  
Neuronal Membrane ◽  
Dependent Manner ◽  
Adrenergic Agonist ◽  
Adult Rat ◽  
Dose Dependent

The role of thyroid hormones (TH) in the normal functioning of adult mammalian brain is unclear. Our studies have identified synaptosomal Na+-K+-ATPase as a TH-responsive physiological parameter in adult rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4) both inhibited Na+-K+-ATPase activity (but not Mg2+-ATPase activity) in similar dose-dependent fashions, while other metabolites of TH were less effective. Although both T3and theβ-adrenergic agonist isoproterenol inhibited Na+-K+-ATPase activity in cerebrocortical synaptosomes in similar ways, theβ-adrenergic receptor blocker propranolol did not counteract the effect of T3. Instead, propranolol further inhibited Na+-K+-ATPase activity in a dose-dependent manner, suggesting that the effect of T3on synaptosomal Na+-K+-ATPase activity was independent ofβ-adrenergic receptor activation. The effect of T3on synaptosomal Na+-K+-ATPase activity was inhibited by theα2-adrenergic agonist clonidine and by glutamate. Notably, both clonidine and glutamate activateGi-proteins of the membrane second messenger system, suggesting a potential mechanism for the inhibition of the effects of TH. In this paper, we provide support for a nongenomic mechanism of action of TH in a neuronal membrane-related energy-linked process for signal transduction in the adult condition.

scholarly journals D-cysteine is an endogenous regulator of neural progenitor cell dynamics in the mammalian brain

2021 ◽  
Vol 118 (39) ◽  
pp. e2110610118
Author(s):  
Evan R. Semenza ◽  
Maged M. Harraz ◽  
Efrat Abramson ◽  
Adarsha P. Malla ◽  
Chirag Vasavda ◽  
...  
Keyword(s):  
High Performance ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Adult Brain ◽  
Luciferase Assay ◽  
Mammalian Brain ◽  
Embryonic Mouse ◽  
Kinase Substrate

d-amino acids are increasingly recognized as important signaling molecules in the mammalian central nervous system. However, the d-stereoisomer of the amino acid with the fastest spontaneous racemization ratein vitro in vitro, cysteine, has not been examined in mammals. Using chiral high-performance liquid chromatography and a stereospecific luciferase assay, we identify endogenous d-cysteine in the mammalian brain. We identify serine racemase (SR), which generates the N-methyl-d-aspartate (NMDA) glutamate receptor coagonist d-serine, as a candidate biosynthetic enzyme for d-cysteine. d-cysteine is enriched more than 20-fold in the embryonic mouse brain compared with the adult brain. d-cysteine reduces the proliferation of cultured mouse embryonic neural progenitor cells (NPCs) by ∼50%, effects not shared with d-serine or l-cysteine. The antiproliferative effect of d-cysteine is mediated by the transcription factors FoxO1 and FoxO3a. The selective influence of d-cysteine on NPC proliferation is reflected in overgrowth and aberrant lamination of the cerebral cortex in neonatal SR knockout mice. Finally, we perform an unbiased screen for d-cysteine–binding proteins in NPCs by immunoprecipitation with a d-cysteine–specific antibody followed by mass spectrometry. This approach identifies myristoylated alanine-rich C-kinase substrate (MARCKS) as a putative d-cysteine–binding protein. Together, these results establish endogenous mammalian d-cysteine and implicate it as a physiologic regulator of NPC homeostasis in the developing brain.

scholarly journals Anatomical development of the cerebellothalamic tract in embryonic mice

2019 ◽  
Author(s):  
Daniël B. Dumas ◽  
Simona V. Gornati ◽  
Youri Adolfs ◽  
Tomomi Shimogori ◽  
R. Jeroen Pasterkamp ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Neurodevelopmental Disorders ◽  
Developmental Disorders ◽  
Light Sheet ◽  
Autism Spectrum ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Wide Field ◽  
Thalamic Nuclei ◽  
Cortical Regions

AbstractCerebellar projections to the thalamus are a pivotal connection in cerebello-cerebral interactions. Apart from its role in coordinating sensorimotor integration in the adult brain, the cerebello-thalamic projection has also been implemented in developmental disorders, such as autism spectrum disorders. Although the development of the cerebellum, thalamus and cerebral cortex have been studied in many species, a detailed description of the ontogeny of the mammalian cerebello-thalamic tract (CbT) is currently missing. Here we investigated the development of the CbT at embryonic stages using transgenic Ntsr1-Cre/Ai14 mice and in utero electroporation (IUE) of wild type mice. Wide-field, confocal and 3D light-sheet imaging of immunohistochemical stainings showed that CbT fibers arrive in the prethalamus between E14.5 and E15.5, but only invade the thalamus after E16.5. We quantified the spread of CbT fibers throughout the various thalamic nuclei and found that at E17.5 and E18.5 the ventrolateral, ventromedial and parafascicular nuclei, but also the mediodorsal and posterior complex become increasingly innervated. Several CbT fiber varicosities colocalize with vGluT2, indicating that already from E18.5 the CbT synapse in various thalamic nuclei. Our results contribute to the construction of a frame of reference on the anatomical development of the CbT, which will help to guide future experiments investigating neurodevelopmental disorders.Significance statementUsing various microscopic approaches, we investigated the anatomical development of the fiber tract between the cerebellum and thalamus, one of the major mammalian brain connections. Our results show that in mice cerebellar axons wait outside of the thalamus from embryonic day (E)15.5 until E17.5 before invading the thalamic complex. Cerebellar axons establish vGluT2-positive synapses at E18.5 throughout various thalamic nuclei, each of which subsequently develops its connections with dedicated cerebral cortical regions. Our data thereby advocate the cerebellar influence on the maturation of the thalamus and connected cerebral cortex. This knowledge can help to guide future experiments into neurodevelopmental disorders affecting cerebello-thalamo-cortical networks.

Zbed3 Is Indispensable for Wnt Signaling Regulation of Cortical Layers Formation in Developing Brain

2021 ◽  
Author(s):  
Xiangbin Ruan ◽  
Gaoao Liu ◽  
Jiafeng Zhou ◽  
Pan Chen ◽  
Changjie Sun ◽  
...  
Keyword(s):  
Radial Glia ◽  
Ventricular Zone ◽  
Ectopic Expression ◽  
Neural Progenitors ◽  
Developing Brain ◽  
Mammalian Brain ◽  
Dependent Manner ◽  
Layer Formation ◽  
Proliferation And Differentiation ◽  
Neuronal Layer

Abstract Wnt/β-catenin signaling plays multiple important roles during mammalian brain development, and it regulates the proliferation and differentiation of neural progenitors in a context-dependent manner and affects neocortex layer formation. However, the specific role of Wnt/β-catenin in neuronal layer fate determination in the neocortex is still unclear. Here, we report that Zbed3, which is a positive regulator of Wnt/β-catenin signaling, colocalizes with β-catenin at the endfeet of radial glia in the ventricular zone of embryo mouse neocortex. Overexpression and knockdown of Zbed3 increased and decreased the activity of Wnt/β-catenin signaling in the neocortex, respectively. Interestingly, knockdown of Zbed3 in vivo could significantly shift neuronal fates from deep layers to upper layers but is not required for the proliferation and differentiation of neural progenitors. Overexpression of Zbed3 led to increased generation of deep-layer neurons without impairing cell cycle exit of neural progenitors. More importantly, knockdown of Zbed3 could effectively block the effects of the ectopic expression of stabilized β-catenin on neocortex layer formation. Hence, our results demonstrate that Zbed3 is indispensable for Wnt/β-catenin signaling regulating neuronal layer fates in the developing brain.

scholarly journals New Insights Into the Intricacies of Proneural Gene Regulation in the Embryonic and Adult Cerebral Cortex

2021 ◽  
Vol 14 ◽  
Author(s):  
Ana-Maria Oproescu ◽  
Sisu Han ◽  
Carol Schuurmans
Keyword(s):  
Stem Cells ◽  
Cerebral Cortex ◽  
Protein Interactions ◽  
Neural Progenitor Cells ◽  
Target Genes ◽  
Brain Regions ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Proneural Gene ◽  
Molecular Control

Historically, the mammalian brain was thought to lack stem cells as no new neurons were found to be made in adulthood. That dogma changed ∼25 years ago with the identification of neural stem cells (NSCs) in the adult rodent forebrain. However, unlike rapidly self-renewing mature tissues (e.g., blood, intestinal crypts, skin), the majority of adult NSCs are quiescent, and those that become ‘activated’ are restricted to a few neurogenic zones that repopulate specific brain regions. Conversely, embryonic NSCs are actively proliferating and neurogenic. Investigations into the molecular control of the quiescence-to-proliferation-to-differentiation continuum in the embryonic and adult brain have identified proneural genes encoding basic-helix-loop-helix (bHLH) transcription factors (TFs) as critical regulators. These bHLH TFs initiate genetic programs that remove NSCs from quiescence and drive daughter neural progenitor cells (NPCs) to differentiate into specific neural cell subtypes, thereby contributing to the enormous cellular diversity of the adult brain. However, new insights have revealed that proneural gene activities are context-dependent and tightly regulated. Here we review how proneural bHLH TFs are regulated, with a focus on the murine cerebral cortex, drawing parallels where appropriate to other organisms and neural tissues. We discuss upstream regulatory events, post-translational modifications (phosphorylation, ubiquitinylation), protein–protein interactions, epigenetic and metabolic mechanisms that govern bHLH TF expression, stability, localization, and consequent transactivation of downstream target genes. These tight regulatory controls help to explain paradoxical findings of changes to bHLH activity in different cellular contexts.

scholarly journals Determinants of drug entry into the developing brain

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1372 ◽  
Author(s):  
Liam Koehn ◽  
Mark Habgood ◽  
Yifan Huang ◽  
Katarzyna Dziegielewska ◽  
Norman Saunders
Keyword(s):  
Abc Transporters ◽  
Chronic Treatment ◽  
Drug Exposure ◽  
Developmental Stages ◽  
Fetal Brain ◽  
Developing Brain ◽  
Adult Brain ◽  
Sprague Dawley ◽  
Age Related ◽  
The Brain

Background: A major concern for clinicians in prescribing medications to pregnant women and neonates is the possibility that drugs might have damaging effects, particularly on long-term brain development. Current understanding of drug permeability at placental and blood-brain barriers during development is poor. In adults, ABC transporters limit many drugs from entering the brain; however, little is known about their function during development. Methods: The transfer of clinically relevant doses of paracetamol (acetaminophen), digoxin and cimetidine into the brain and cerebrospinal fluid (CSF) was estimated using radiolabelled drugs in Sprague Dawley rats at three developmental stages: E19, P4 and adult. Drugs were applied intraperitoneally either acutely or following chronic exposure (for five days). Entry into brain, CSF and transfer across the placenta was measured and compared to three markers (L-glucose, sucrose, glycerol) that cross barriers by “passive diffusion”. The expression of ABC transporters in the brain, choroid plexus and placenta was estimated using RT-qPCR. Results: All three drugs entered the developing brain and CSF in higher amounts than the adult brain and CSF. Comparisons with “passive” permeability markers suggested that this might be due to age-related differences in the functional capacity of ABC-efflux mechanisms. In adult animals, chronic treatment reduced digoxin (12% to 5%, p<0.01) and paracetamol (30% to 21%, p<0.05) entry compared to acute treatment, with the decrease in digoxin entry correlating with up-regulation of efflux transporter abcb1a (PGP). In fetal and newborn animals, no gene up-regulation or transfer decreases were observed. Instead, chronic paracetamol treatment resulted in increased transfer into the fetal brain (66% to 104%, p<0.001). Conclusions: These results suggest that the developing brain may be more at risk from acute drug exposure than the adult brain due to reduced efflux capacity and at greater risk from chronic treatment due to a lack of efflux mechanism regulatory capacity.

scholarly journals Reelin in the Years: Controlling Neuronal Migration and Maturation in the Mammalian Brain

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Gabriella D'Arcangelo
Keyword(s):  
Neuronal Migration ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Adult Brain ◽  
Synaptic Activity ◽  
Mammalian Brain ◽  
Layer Formation ◽  
Essential Factor ◽  
Multifunctional Protein ◽  
And Function

The extracellular protein Reelin was initially identified as an essential factor in the control of neuronal migration and layer formation in the developing mammalian brain. In the years following its discovery, however, it became clear that Reelin is a multifunctional protein that controls not only the positioning of neurons in the developing brain, but also their growth, maturation, and synaptic activity in the adult brain. In this review, we will highlight the major discoveries of the biological activities of Reelin and the underlying molecular mechanisms that affect the development and function of the mammalian brain, from embryonic ages to adulthood.

scholarly journals Global Epigenomic Reconfiguration During Mammalian Brain Development

Science ◽  
2013 ◽  
Vol 341 (6146) ◽  
pp. 1237905 ◽  
Author(s):  
Ryan Lister ◽  
Eran A. Mukamel ◽  
Joseph R. Nery ◽  
Mark Urich ◽  
Clare A. Puddifoot ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Adult Development ◽  
Fetal Brain ◽  
Brain Cell ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Dominant Form ◽  
Single Base ◽  
Single Base Resolution

DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.

scholarly journals An architectonic type principle in the development of laminar patterns of cortico-cortical connections

2021 ◽  
Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag
Keyword(s):  
Structural Connectivity ◽  
Macaque Monkey ◽  
Brain Regions ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Cortical Connections ◽  
Cortical Projections ◽  
Structural Connections ◽  
High Degree ◽  
The Brain

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.

scholarly journals Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes

2021 ◽  
Author(s):  
Rachel L. Leon ◽  
Imran N. Mir ◽  
Christina L. Herrera ◽  
Kavita Sharma ◽  
Catherine Y. Spong ◽  
...  
Keyword(s):  
Brain Development ◽  
Congenital Heart ◽  
Fetal Brain ◽  
In Utero ◽  
Structure And Function ◽  
Brain Growth ◽  
Neurodevelopmental Outcomes ◽  
Fetal Brain Development ◽  
And Function

Abstract Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta–heart–brain connection. Impact Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.

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