scholarly journals Molecular mechanism of brain development and neurodevelopmental disorders regulated be neuroimmune system

2021 ◽  
Vol 156 (2) ◽  
pp. 81-84
Author(s):  
Shogo Tanabe ◽  
Rieko Muramatsu
Keyword(s):  
Brain Development ◽  
Molecular Mechanism ◽  
Neurodevelopmental Disorders ◽  
Neuroimmune System

scholarly journals Histamine, Neuroinflammation and Neurodevelopment: A Review

2021 ◽  
Vol 15 ◽  
Author(s):  
Elliott Carthy ◽  
Tommas Ellender
Keyword(s):  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Histamine Receptor ◽  
Future Research ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Inflammatory Processes ◽  
Preclinical And Clinical Studies

The biogenic amine, histamine, has been shown to critically modulate inflammatory processes as well as the properties of neurons and synapses in the brain, and is also implicated in the emergence of neurodevelopmental disorders. Indeed, a reduction in the synthesis of this neuromodulator has been associated with the disorders Tourette’s syndrome and obsessive-compulsive disorder, with evidence that this may be through the disruption of the corticostriatal circuitry during development. Furthermore, neuroinflammation has been associated with alterations in brain development, e.g., impacting synaptic plasticity and synaptogenesis, and there are suggestions that histamine deficiency may leave the developing brain more vulnerable to proinflammatory insults. While most studies have focused on neuronal sources of histamine it remains unclear to what extent other (non-neuronal) sources of histamine, e.g., from mast cells and other sources, can impact brain development. The few studies that have started exploring this in vitro, and more limited in vivo, would indicate that non-neuronal released histamine and other preformed mediators can influence microglial-mediated neuroinflammation which can impact brain development. In this Review we will summarize the state of the field with regard to non-neuronal sources of histamine and its impact on both neuroinflammation and brain development in key neural circuits that underpin neurodevelopmental disorders. We will also discuss whether histamine receptor modulators have been efficacious in the treatment of neurodevelopmental disorders in both preclinical and clinical studies. This could represent an important area of future research as early modulation of histamine from neuronal as well as non-neuronal sources may provide novel therapeutic targets in these disorders.

scholarly journals Brain Organoids as Tools for Modeling Human Neurodevelopmental Disorders

Physiology ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 365-375 ◽  
Author(s):  
Jason W. Adams ◽  
Fernanda R. Cugola ◽  
Alysson R. Muotri
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Technological Advancement ◽  
Neurodevelopmental Disease ◽  
Human Brain Development ◽  
Therapeutic Development ◽  
Innovative Tool

Brain organoids recapitulate in vitro the specific stages of in vivo human brain development, thus offering an innovative tool by which to model human neurodevelopmental disease. We review here how brain organoids have been used to study neurodevelopmental disease and consider their potential for both technological advancement and therapeutic development.

Sox2 protects neural stem cells from apoptosis via up-regulating survivin expression

2013 ◽  
Vol 450 (3) ◽  
pp. 459-468 ◽  
Author(s):  
Ruopeng Feng ◽  
Shixin Zhou ◽  
Yinan Liu ◽  
Daijun Song ◽  
Zhilin Luan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Brain Development ◽  
Molecular Mechanism ◽  
Cell Apoptosis ◽  
Survivin Expression ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Self Renewal

The transcription factor Sox2 [SRY (sex-determining region Y)-box 2] is essential for the regulation of self-renewal and homoeostasis of NSCs (neural stem cells) during brain development. However, the downstream targets of Sox2 and its underlying molecular mechanism are largely unknown. In the present study, we found that Sox2 directly up-regulates the expression of survivin, which inhibits the mitochondria-dependent apoptotic pathway in NSCs. Although overexpression of Sox2 elevates survivin expression, knockdown of Sox2 results in a decrease in survivin expression, thereby initiating the mitochondria-dependent apoptosis related to caspase 9 activation. Furthermore, cell apoptosis owing to knockdown of Sox2 can be rescued by ectopically expressing survivin in NSCs as well as in the mouse brain, as demonstrated by an in utero-injection approach. In short, we have found a novel Sox2/survivin pathway that regulates NSC survival and homoeostasis, thus revealing a new mechanism of brain development, neurological degeneration and such aging-related disorders.

scholarly journals Impaired αVβ8 and TGFβ signaling lead to microglial dysmaturation and neuromotor dysfunction

2019 ◽  
Vol 216 (4) ◽  
pp. 900-915 ◽  
Author(s):  
Thomas D. Arnold ◽  
Carlos O. Lizama ◽  
Kelly M. Cautivo ◽  
Nicolas Santander ◽  
Lucia Lin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Tgfβ Signaling ◽  
Critical Determinant ◽  
Conditional Deletion ◽  
Stepwise Development ◽  
The Central Nervous System

Microglia play a pivotal role in the coordination of brain development and have emerged as a critical determinant in the progression of neurodegenerative diseases; however, the role of microglia in the onset and progression of neurodevelopmental disorders is less clear. Here we show that conditional deletion of αVβ8 from the central nervous system (Itgb8ΔCNS mice) blocks microglia in their normal stepwise development from immature precursors to mature microglia. These “dysmature” microglia appear to result from reduced TGFβ signaling during a critical perinatal window, are distinct from microglia with induced reduction in TGFβ signaling during adulthood, and directly cause a unique neurodevelopmental syndrome characterized by oligodendrocyte maturational arrest, interneuron loss, and spastic neuromotor dysfunction. Consistent with this, early (but not late) microglia depletion completely reverses this phenotype. Together, these data identify novel roles for αVβ8 and TGFβ signaling in coordinating microgliogenesis with brain development and implicate abnormally programmed microglia or their products in human neurodevelopmental disorders that share this neuropathology.

scholarly journals Gene regulatory networks underlying human microglia maturation

2021 ◽  
Author(s):  
Nicole G Coufal ◽  
Christopher Glass ◽  
Claudia Han ◽  
Rick Z. Li ◽  
Emily Hansen ◽  
...  
Keyword(s):  
Brain Development ◽  
Single Cell ◽  
Gene Regulatory Networks ◽  
Neurodevelopmental Disorders ◽  
Regulatory Networks ◽  
Critical Time ◽  
Open Chromatin ◽  
Potential Contribution ◽  
Gene Regulatory ◽  
The Brain

The fetal period is a critical time for brain development, characterized by neurogenesis, neural migration, and synaptogenesis(1-3). Microglia, the tissue resident macrophages of the brain, are observed as early as the fourth week of gestation4 and are thought to engage in a variety of processes essential for brain development and homeostasis(5-11). Conversely, microglia phenotypes are highly regulated by the brain environment(12-14). Mechanisms by which human brain development influences the maturation of microglia and microglia potential contribution to neurodevelopmental disorders remain poorly understood. Here, we performed transcriptomic analysis of human fetal and postnatal microglia and corresponding cortical tissue to define age-specific brain environmental factors that may drive microglia phenotypes. Comparative analysis of open chromatin profiles using bulk and single-cell methods in conjunction with a new computational approach that integrates epigenomic and single-cell RNA-seq data allowed decoding of cellular heterogeneity with inference of subtype- and development stage-specific transcriptional regulators. Interrogation of in vivo and in vitro iPSC-derived microglia models provides evidence for roles of putative instructive signals and downstream gene regulatory networks which establish human-specific fetal and postnatal microglia gene expression programs and potentially contribute to neurodevelopmental disorders.

scholarly journals Typical and atypical brain development: a review of neuroimaging studies

2013 ◽  
Vol 15 (3) ◽  
pp. 359-384 ◽  
Keyword(s):  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Fragile X ◽  
Early Adulthood ◽  
22Q11.2 Deletion Syndrome ◽  
Developmental Trajectory ◽  
Deletion Syndrome ◽  
Effective Interventions ◽  
And Function ◽  
The Brain

In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

2017 ◽  
Vol 177 (1) ◽  
pp. R27-R36 ◽  
Author(s):  
Stine Linding Andersen ◽  
Allan Carlé ◽  
Jesper Karmisholt ◽  
Inge Bülow Pedersen ◽  
Stig Andersen
Keyword(s):  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Fetal Programming ◽  
Thyroid Dysfunction ◽  
Child Outcomes ◽  
Fetal Brain ◽  
Epidemiological Studies ◽  
Fetal Brain Development ◽  
Maternal Thyroid ◽  
Exposures During Pregnancy

Fetal programming is a long-standing, but still evolving, concept that links exposures during pregnancy to the later development of disease in the offspring. A fetal programming effect has been considered within different endocrine axes and in relation to different maternal endocrine diseases. In this critical review, we describe and discuss the hypothesis of fetal programming by maternal thyroid dysfunction in the context of fetal brain development and neurodevelopmental disorders in the offspring. Thyroid hormones are important regulators of early brain development, and evidence from experimental and observational human studies have demonstrated structural and functional abnormalities in the brain caused by the lack or excess of thyroid hormone during fetal brain development. The hypothesis that such abnormalities introduced during early fetal brain development increase susceptibility for the later onset of neurodevelopmental disorders in the offspring is biologically plausible. However, epidemiological studies on the association between maternal thyroid dysfunction and long-term child outcomes are observational in design, and are challenged by important methodological aspects.

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