scholarly journals critical role of astrogenesis and neurodevelopment in Fragile X Syndrome and Rett Syndrome

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
John Paul Oliveria ◽  
Zhuo Jun Li
Keyword(s):  
Fragile X Syndrome ◽  
Rett Syndrome ◽  
Fragile X ◽  
Critical Role ◽  
Notch Pathway ◽  
Janus Kinase ◽  
Future Research ◽  
Genetic Mutations ◽  
And Function ◽  
The Brain

Astrocytes play an important role in the development of functional neural circuits in the brain. They are responsible for coordinating synapse formation and function, axon guidance, and ensuring neuronal survival. Normal astrogenesis begins during late gestation. Neural stem cells (NSCs) become primarily gliogenic and differentiate to become astrocyte precursors. Through local proliferation and functional maturation, the precursors develop into mature astrocytes, which can either be fibrous or protoplasmic. Astrogenesis is regulated by both cell intrinsic programs and cell extrinsic cues. Intrinsic chromatin changes, such as demethylation of astrocyte-specific genes, allows the NSCs to become responsive to astrocyte-inducing exogenous cues. These cues involve a collaboration of multiple pathways, namely the Notch pathway, the bone morphogenetic protein (BMP) signaling pathway, interleukin-6 (IL-6) signaling, and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway. Together, they allow for normal astrogenesis to occur. However, disruption to these pathways lead to abnormal astrocyte development and results in pathologies such as the Fragile X Syndrome (FXS) and Rett Syndrome (RS). Both neurodevelopmental disorders are a result of genetic mutations that causes either transcriptional silence or transcriptional activation at inappropriate stages during development. These genetic mutations result in depressed astrocyte function in FXS, and the overexcitement of astrocytes in RS. The current hypothesis under investigation is that altered gene transcription during neurodevelopment disrupts astrogenesis, and subsequently, the behavior and function of mature astrocytes in the brain. Future research should focus on understanding the timing of the transition from neurogenesis to astrogenesis and identifying astrocyte-specific markers that are critical to its function in neurodevelopment.

scholarly journals Fragile X syndrome patient-derived neurons developing in the mouse brain show FMR1 -dependent phenotypes

2021 ◽  
Author(s):  
Marine A Krzisch ◽  
Hao A Wu ◽  
Bingbing Yuan ◽  
Troy W. Whitfield ◽  
X. Shawn Liu ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Neuronal Development ◽  
Fragile X ◽  
In Vitro Models ◽  
Synaptic Activity ◽  
Human Neurons ◽  
Induced Pluripotent ◽  
And Function ◽  
The Brain

Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The transplanted cells populated the brain and a proportion differentiated into neurons and glial cells. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons after an initial delay. Additionally, increased percentages of Arc- and Egr1-positive FXS neurons and wider dendritic protrusions of mature FXS striatal medium spiny neurons pointed to an increase in synaptic activity and synaptic strength as compared to control. This transplantation approach provides new insights into the alterations of neuronal development in FXS by facilitating physiological development of cells in a 3D context, and could be used to test new therapeutic compounds correcting neuronal development defects in FXS.

Human-mouse chimeric Fragile X syndrome model reveals FMR1-dependent neuronal phenotypes

2020 ◽  
Author(s):  
Marine Krzisch ◽  
Hao Wu ◽  
Bingbing Yuan ◽  
Troy Whitfield ◽  
Shawn Liu ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Neuronal Development ◽  
Fragile X ◽  
In Vitro Models ◽  
Synaptic Activity ◽  
Human Neurons ◽  
Induced Pluripotent ◽  
And Function ◽  
The Brain

Abstract Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The cells populated the brain and differentiated into neurons and astrocytes. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons, an increased proportion of Arc-positive FXS neurons and increased dendritic protrusion width of FXS striatal medium spiny neurons. Our data show faster maturation and suggest increased synaptic activity and synaptic strength of FXS transplanted neurons. This model provides new insights into the alterations in FXS neuronal development.

scholarly journals Drosophila Fragile X Protein, DFXR, Regulates Neuronal Morphology and Function in the Brain

Neuron ◽  
2002 ◽  
Vol 34 (6) ◽  
pp. 961-972 ◽  
Author(s):  
Joannella Morales ◽  
P.Robin Hiesinger ◽  
Andrew J. Schroeder ◽  
Kazuhiko Kume ◽  
Patrik Verstreken ◽  
...  
Keyword(s):  
Fragile X ◽  
Neuronal Morphology ◽  
X Protein ◽  
And Function ◽  
The Brain

scholarly journals Thiamine status, metabolism and application in dairy cows: a review

2018 ◽  
Vol 120 (5) ◽  
pp. 491-499 ◽  
Author(s):  
Xiaohua Pan ◽  
Xuemei Nan ◽  
Liang Yang ◽  
Linshu Jiang ◽  
Benhai Xiong
Keyword(s):  
Dairy Cows ◽  
Thiamine Deficiency ◽  
Critical Role ◽  
Thiamine Pyrophosphate ◽  
Future Research ◽  
Nutrient Metabolism ◽  
Beneficial Effects ◽  
Current State ◽  
Ruminal Epithelium ◽  
And Function

AbstractAs the co-enzyme of pyruvate dehydrogenase andα-ketoglutarate dehydrogenase, thiamine plays a critical role in carbohydrate metabolism in dairy cows. Apart from feedstuff, microbial thiamine synthesis in the rumen is the main source for dairy cows. However, the amount of ruminal thiamine synthesis, which is influenced by dietary N levels and forage to concentrate ratio, varies greatly. Notably, when dairy cows are overfed high-grain diets, subacute ruminal acidosis (SARA) occurs and results in thiamine deficiency. Thiamine deficiency is characterised by decreased ruminal and blood thiamine concentrations and an increased blood thiamine pyrophosphate effect to >45 %. Thiamine deficiency caused by SARA is mainly related to the increased thiamine requirement during high grain feeding, decreased bacterial thiamine synthesis in the rumen, increased thiamine degradation by thiaminase, and decreased thiamine absorption by transporters. Interestingly, thiamine deficiency can be reversed by exogenous thiamine supplementation in the diet. Besides, thiamine supplementation has beneficial effects in dairy cows, such as increased milk and component production and attenuated SARA by improving rumen fermentation, balancing bacterial community and alleviating inflammatory response in the ruminal epithelium. However, there is no conclusive dietary thiamine recommendation for dairy cows, and the impacts of thiamine supplementation on protozoa, solid-attached bacteria, rumen wall-adherent bacteria and nutrient metabolism in dairy cows are still unclear. This knowledge is critical to understand thiamine status and function in dairy cows. Overall, the present review described the current state of knowledge on thiamine nutrition in dairy cows and the major problems that must be addressed in future research.

Responsive Parenting as a Target for Telehealth Language Interventions in Fragile X Syndrome: Implications for Scalability and Best Practices

2021 ◽  
Vol 42 (04) ◽  
pp. 287-300
Author(s):  
Lauren Bullard ◽  
Leonard Abbeduto
Keyword(s):  
Best Practices ◽  
Language Development ◽  
Fragile X Syndrome ◽  
Child Language ◽  
Fragile X ◽  
Future Research ◽  
Dyadic Relationship ◽  
Video Teleconferencing ◽  
Treatment Gains ◽  
Speech And Language Development

AbstractThis review highlights the ways in which telehealth procedures can be implemented to help bridge the research-to-practice gap in supporting developmental outcomes for youth with fragile X syndrome (FXS). We review how the literature to date has informed potential treatment targets in the areas of speech and language development with a focus on understanding and supporting the dyadic relationship between the child and their biological mother, who is also impacted biologically. Notably, parental responsivity is an area that is strongly related to child language outcomes, both early and into adolescence, and thus, it is an important treatment target for subsequent interventions. To date, several parent-implemented interventions have been done in FXS across a broad age range (2–17-year-olds) all showing support not only that parents are successful in learning responsive strategies but also that there are subsequent impacts to child language development. Moreover, these interventions were successfully implemented at a distance through telehealth procedures including video teleconferencing and shared recordings of parent–child interactions. This review also addresses potential moderators of treatment gains. Implications for scaling such interventions in the future as well as best practices for incorporating telehealth procedures into future research and intervention programs are also discussed.

Form and Function in Cells of the Brain

The Neuron ◽  
2015 ◽  
pp. 23-38
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Critical Role ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Cell Body ◽  
Long Distance ◽  
Form And Function ◽  
And Function ◽  
The Brain

This chapter examines unique mechanisms that the neuron has evolved to establish and maintain the form required for its specialized signaling functions. Unlike some other organs, the brain contains a variety of cell types including several classes of glial cells, which play a critical role in the formation of the myelin sheath around axons and may be involved in immune responses, synaptic transmission, and long-distance calcium signaling in the brain. Neurons share many features in common with other cells (including glia), but they are distinguished by their highly asymmetrical shapes. The neuronal cytoskeleton is essential for establishing this cell shape during development and for maintaining it in adulthood. The process of axonal transport moves vesicles and other organelles to regions remote from the neuronal cell body. Proteins such as kinesin and dynein, called molecular motors, make use of the energy released by hydrolysis of ATP to drive axonal transport.

scholarly journals A metabolomic and systems biology perspective on the brain of the Fragile X syndrome mouse model

2011 ◽  
Vol 21 (12) ◽  
pp. 2190-2202 ◽  
Author(s):  
L. Davidovic ◽  
V. Navratil ◽  
C. M. Bonaccorso ◽  
M. V. Catania ◽  
B. Bardoni ◽  
...  
Keyword(s):  
Systems Biology ◽  
Mouse Model ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
The Brain

scholarly journals Narrating Disability, Narrating Religious Practice: Reconciliation and Fragile X Syndrome

2010 ◽  
Vol 48 (2) ◽  
pp. 99-111 ◽  
Author(s):  
Marsha Michie ◽  
Debra Skinner
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Religious Practice ◽  
Illness Narratives ◽  
Future Research ◽  
Semistructured Interviews ◽  
Religious Perspectives

Abstract This article examines the place of religion in the narratives of mothers of children with fragile X syndrome. In semistructured interviews, a majority of women combined narratives of religious practice with illness narratives, interpreting their children's disabilities within a religious framework. Informed by Arthur Frank's (1995) concept of “wounded storytellers,” the authors articulate a reconciliation narrative that mothers commonly used to describe their transition from viewing disability as a burden or challenge to seeing it as a blessing, or as a part of God's purpose or plan for their lives. The authors discuss the significance of narrative for better understanding religious perspectives on disability and conclude with the implications of these findings for practitioners and future research.

scholarly journals Novel Insight Into the Development and Function of Hypopharyngeal Glands in Honey Bees

2021 ◽  
Vol 11 ◽  
Author(s):  
Saboor Ahmad ◽  
Shahmshad Ahmed Khan ◽  
Khalid Ali Khan ◽  
Jianke Li
Keyword(s):  
Honey Bees ◽  
Future Research ◽  
Factors Affecting ◽  
Hypopharyngeal Glands ◽  
And Function ◽  
First Time ◽  
The Brain ◽  
Insight Into ◽  
Made In

Hypopharyngeal glands (HGs) are the most important organ of hymenopterans which play critical roles for the insect physiology. In honey bees, HGs are paired structures located bilaterally in the head, in front of the brain between compound eyes. Each gland is composed of thousands of secretory units connecting to secretory duct in worker bees. To better understand the recent progress made in understanding the structure and function of these glands, we here review the ontogeny of HGs, and the factors affecting the morphology, physiology, and molecular basis of the functionality of the glands. We also review the morphogenesis of HGs in the pupal and adult stages, and the secretory role of the glands across the ages for the first time. Furthermore, recent transcriptome, proteome, and phosphoproteome analyses have elucidated the potential mechanisms driving the HGs development and functionality. This adds a comprehensive novel knowledge of the development and physiology of HGs in honey bees over time, which may be helpful for future research investigations.

scholarly journals Projections of the Mouse Primary Visual Cortex

2021 ◽  
Vol 15 ◽  
Author(s):  
Arbora Resulaj
Keyword(s):  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Visual Processing ◽  
Brain Area ◽  
Critical Role ◽  
Future Research ◽  
Projection Neurons ◽  
Challenges And Opportunities ◽  
And Function ◽  
To Receive

Lesion or damage to the primary visual cortex (V1) results in a profound loss of visual perception in humans. Similarly, in mice, optogenetic silencing of V1 profoundly impairs discrimination of orientated gratings. V1 is thought to have such a critical role in perception in part due to its position in the visual processing hierarchy. It is the first brain area in the neocortex to receive visual input, and it distributes this information to more than 18 brain areas. Here I review recent advances in our understanding of the organization and function of the V1 projections in the mouse. This progress is in part due to new anatomical and viral techniques that allow for efficient labeling of projection neurons. In the final part of the review, I conclude by highlighting challenges and opportunities for future research.

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