scholarly journals Cerebellar Morphology and Behavioral Profiles in Mice Lacking Heparan Sulfate Ndst Gene Function

2020 ◽  
Vol 8 (3) ◽  
pp. 13
Author(s):  
Lars Lewejohann ◽  
Srinivas R. Pallerla ◽  
Rebecca S. Schreiber ◽  
Joanna Gerula ◽  
Kay Grobe
Keyword(s):  
Purkinje Cell ◽  
Heparan Sulfate ◽  
Gene Function ◽  
System Development ◽  
Nervous System Development ◽  
Adult Brain ◽  
Reproductive Capacity ◽  
Cell Protein ◽  
Brain Physiology ◽  
Mutant Female

Disruption of the Heparan sulfate (HS)-biosynthetic gene N-acetylglucosamine N-Deacetylase/N-sulfotransferase 1 (Ndst1) during nervous system development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. However, the role of Ndst function in adult brain physiology is less explored. Therefore, we generated mice bearing a Purkinje-cell-specific deletion in Ndst1 gene function by using Cre/loxP technology under the control of the Purkinje cell protein 2 (Pcp2/L7) promotor, which results in HS undersulfation. We observed that mutant mice did not show overt changes in the density or organization of Purkinje cells in the adult cerebellum, and behavioral tests also demonstrated normal cerebellar function. This suggested that postnatal Purkinje cell development and homeostasis are independent of Ndst1 function, or that impaired HS sulfation upon deletion of Ndst1 function may be compensated for by other Purkinje cell-expressed Ndst isoforms. To test the latter possibility, we additionally deleted the second Purkinje-cell expressed Ndst family member, Ndst2. This selectively abolished reproductive capacity of compound mutant female, but not male, mice, suggesting that ovulation, gestation, or female reproductive behavior specifically depends on Ndst-dependent HS sulfation in cells types that express Cre under Pcp2/L7 promotor control.

scholarly journals Insulin and insulinlike growth factor 1 (IGF-1) receptors during central nervous system development: expression of two immunologically distinct IGF-1 receptor beta subunits.

1989 ◽  
Vol 9 (7) ◽  
pp. 2806-2817 ◽  
Author(s):  
R S Garofalo ◽  
O M Rosen
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
System Development ◽  
Fetal Brain ◽  
Nervous System Development ◽  
Adult Brain ◽  
Beta Subunit ◽  
Tyrosine Kinase Domain ◽  
Beta Subunits ◽  
Insulinlike Growth Factor

Insulin and insulinlike growth factor 1 (IGF-1) receptors are present in brain, yet their function remains obscure. Expression of these tyrosine kinase-bearing growth factor receptors during rat brain development was examined by using three antipeptide antibodies directed against epitopes in the beta subunits (AbP2, AbP4, and AbP5). All three antibodies recognized both insulin and IGF-1 receptors. Membranes were prepared from fetal brains (14 to 21 days of gestation), neonatal brain (postnatal day 1), and adult brain. Immunoblot analyses using AbP4 and AbP5 revealed a 92-kilodalton (kDa) protein that corresponded to the beta subunit of the insulin and IGF-1 receptors. Densitometric scanning of immunoblots indicated that receptor proteins were 4- to 10-fold more abundant in fetal brain membranes than in membranes from adult brain. Expression was highest during 16 to 18 days of gestation and declined thereafter to the relatively low level found in adult brain. Immunoblot analyses with AbP2 as well as ligand-activated receptor autophosphorylation revealed an additional protein of 97 kDa. This protein was phosphorylated in response to IGF-1 and was not directly recognized by AbP4 or AbP5. The covalent association of the 97-kDa protein with the 92-kDa beta subunit was indicated by the ability of AbP4 and AbP5 to immunoprecipitate both proteins under nonreducing conditions but only the 92-kDa protein after reduction. In contrast, AbP2 immunoprecipitated both proteins regardless of their association. This immunospecificity remained unchanged after deglycosylation of the isolated proteins. Two-dimensional tryptic phosphopeptide analysis showed that the 92- and 97-kDa subunits of the IGF-1 receptor are related but distinct proteins. Taken together, the data suggest that the 92- and 97-kDa subunits differ in primary amino acid sequence. Thus, two distinct beta subunits may be present in a single IGF-1 receptor in brain. These subunits have in common an epitope recognized by an antibody to the tyrosine kinase domain (AbP2) but differ in regions thought to be important in receptor kinase regulation and signal transduction.

scholarly journals Complex Cooperative Functions of Heparan Sulfate Proteoglycans Shape Nervous System Development in Caenorhabditis elegans

2014 ◽  
Vol 4 (10) ◽  
pp. 1859-1870 ◽  
Author(s):  
Carlos A. Díaz-Balzac ◽  
María I. Lázaro-Peña ◽  
Eillen Tecle ◽  
Nathali Gomez ◽  
Hannes E. Bülow
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Heparan Sulfate ◽  
System Development ◽  
Nervous System Development ◽  
Heparan Sulfate Proteoglycans

scholarly journals Cell-type specific patterned stimulus-independent neuronal activity in the Drosophila visual system during synapse formation

2018 ◽  
Author(s):  
Orkun Akin ◽  
Bryce T. Bajar ◽  
Mehmet F. Keles ◽  
Mark A. Frye ◽  
S. Lawrence Zipursky
Keyword(s):  
Visual System ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Specific Activity ◽  
System Development ◽  
Nervous System Development ◽  
Adult Brain ◽  
Cell Type ◽  
Cell Type Specific

SummaryStereotyped synaptic connections define the neural circuits of the brain. In vertebrates, stimulus-independent activity contributes to neural circuit formation. It is unknown whether this type of activity is a general feature of nervous system development. Here, we report patterned, stimulus-independent neural activity in the Drosophila visual system during synaptogenesis. Using in vivo calcium, voltage, and glutamate imaging, we found that all neurons participate in this spontaneous activity, which is characterized by brain-wide periodic active and silent phases. Glia are active in a complementary pattern. Each of the 15 examined of the over 100 specific neuron types in the fly visual system exhibited a unique activity signature. The activity of neurons that are synaptic partners in the adult was highly correlated during development. We propose that this cell type-specific activity coordinates the development of the functional circuitry of the adult brain.

13-cis-Retinoic Acid Alters Intracellular Serotonin, Increases 5-HT1A Receptor, and Serotonin Reuptake Transporter Levels In Vitro

2007 ◽  
Vol 232 (9) ◽  
pp. 1195-1203 ◽  
Author(s):  
Kally C. O’Reilly ◽  
Simon Trent ◽  
Sarah J. Bailey ◽  
Michelle A. Lane
Keyword(s):  
Retinoic Acid ◽  
Cell Line ◽  
Serotonin Reuptake ◽  
System Development ◽  
Chronic Administration ◽  
Nervous System Development ◽  
Adult Brain ◽  
Adolescent Male ◽  
Serotonin Reuptake Transporter

In addition to their established role in nervous system development, vitamin A and related retinoids are emerging as regulators of adult brain function. Accutane (13- cis-retinoic acid, isotretinoin) treatment has been reported to increase depression in humans. Recently, we showed that chronic administration of 13- cis-retinoic acid (13- cis-RA) to adolescent male mice increased depression-related behaviors. Here, we have examined whether 13- cis-RA regulates components involved in serotonergic neurotransmission in vitro. We used the RN46A-B14 cell line, derived from rat embryonic raphe nuclei. This cell line synthesizes serotonin (5-hydroxytryptamine, 5-HT) and expresses the 5-HT1A receptor and the serotonin reuptake transporter (SERT). Cells were treated with 0, 2.5, or 10 μ M 13- cis-RA for 48 or 96 hrs, and the levels of 5-HT; its metabolite, 5-hydroxyindoleacetic acid (5HIAA); 5-HT1A receptor; and SERT were determined. Treatment with 13- cis-RA for 96 hrs increased the intracellular levels of 5-HT and tended to increase intra-cellular 5HIAA levels. Furthermore, 48 hrs of treatment with 2.5 and 10 μ M 13- cis-RA significantly increased 5-HT1A protein to 168.5 ± 20.0% and 148.7 ± 2.2% of control respectively. SERT protein levels were significantly increased to 142.5 ± 11.1% and 119.2 ± 3.6% of control by 48 hrs of treatment with 2.5 and 10 μ M of 13- cis-RA respectively. Increases in both 5-HT1A receptor and SERT proteins may lead to decreased serotonin availability at synapses. Such an effect of 13- cis-RA could contribute to the increased depression-related behaviors we have shown in mice.

scholarly journals The Hidden Side of NCAM Family: NCAM2, a Key Cytoskeleton Organization Molecule Regulating Multiple Neural Functions

2021 ◽  
Vol 22 (18) ◽  
pp. 10021
Author(s):  
Antoni Parcerisas ◽  
Alba Ortega-Gascó ◽  
Lluís Pujadas ◽  
Eduardo Soriano
Keyword(s):  
Nervous System ◽  
Calcium Influx ◽  
System Development ◽  
Nervous System Development ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Neuronal Morphogenesis ◽  
Cytoskeleton Organization ◽  
New Therapeutic Approaches ◽  
Neural Cell Adhesion

Although it has been over 20 years since Neural Cell Adhesion Molecule 2 (NCAM2) was identified as the second member of the NCAM family with a high expression in the nervous system, the knowledge of NCAM2 is still eclipsed by NCAM1. The first studies with NCAM2 focused on the olfactory bulb, where this protein has a key role in axonal projection and axonal/dendritic compartmentalization. In contrast to NCAM1, NCAM2’s functions and partners in the brain during development and adulthood have remained largely unknown until not long ago. Recent studies have revealed the importance of NCAM2 in nervous system development. NCAM2 governs neuronal morphogenesis and axodendritic architecture, and controls important neuron-specific processes such as neuronal differentiation, synaptogenesis and memory formation. In the adult brain, NCAM2 is highly expressed in dendritic spines, and it regulates synaptic plasticity and learning processes. NCAM2’s functions are related to its ability to adapt to the external inputs of the cell and to modify the cytoskeleton accordingly. Different studies show that NCAM2 interacts with proteins involved in cytoskeleton stability and proteins that regulate calcium influx, which could also modify the cytoskeleton. In this review, we examine the evidence that points to NCAM2 as a crucial cytoskeleton regulation protein during brain development and adulthood. This key function of NCAM2 may offer promising new therapeutic approaches for the treatment of neurodevelopmental diseases and neurodegenerative disorders.

31 Gametic Incompatibility: Improving the Success of Mate Allocation in Dairy Cattle

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 16-17
Author(s):  
Audrey A A Martin ◽  
Samir Id-Lahoucine ◽  
Dan Tulpan ◽  
Stephen J Leblanc ◽  
Angela Cánovas ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
System Development ◽  
Enrichment Analysis ◽  
Mendelian Inheritance ◽  
Nervous System Development ◽  
Transmission Ratio Distortion ◽  
Reproductive Capacity ◽  
Pathway Enrichment Analysis ◽  
Inbreeding Coefficients ◽  
Offspring Genotype

Abstract In the dairy industry, mate allocation is mainly based on the parents’ breeding values and inbreeding coefficients aiming to achieve the producer’s breeding goal. With artificial insemination, the portfolio of sires to choose from is large and the quality of the semen doses is standardized. However, not all sire-dam matings are equally likely to produce a successful pregnancy. Among other reproduction issues, the success of a mating could vary due to the incompatibility of gametes coming from the sire and the dam and could influence the fertilization’s success, additionally to the reproductive capacity of the parents. Considering the gametic incompatibility of the potential parents could be a novel option to improve mating plans. Under the hypothesis that gametic incompatibility has a significant effect on reproduction and reduces the odds of fertilization and pregnancy, this study aimed to determine the genetic background of gametic incompatibility. Transmission ratio distortion (TRD), which detects deviations from Mendelian inheritance expectations, is commonly used to identify deleterious mutations. We adapted the TRD model by including an interaction effect between the gametes leading to the offspring genotype to detect regions with TRD effects and gametic incompatibility. Our dataset contained 436,651 genotyped (50K SNP) Canadian Holstein cattle from 283,817 parents-offspring trios. A total of 482 regions with TRD containing 671 positional genes were found. The functional analysis detected biological pathways associated with uterus development, embryonic skeletal system development, and nervous system development. Additionally, gene ontology terms from the topology-based pathway enrichment analysis were mostly related to the steroid hormones signalling pathway. Although difficult, genes specific to gametic incompatibility could be differentiated from genes underlying other reproduction processes by refining the genetic regions with TRD. With further investigation, we will provide new information to improve mate allocation for the dairy cattle industry.

Environment and Brain Plasticity: Towards an Endogenous Pharmacotherapy

2014 ◽  
Vol 94 (1) ◽  
pp. 189-234 ◽  
Author(s):  
Alessandro Sale ◽  
Nicoletta Berardi ◽  
Lamberto Maffei
Keyword(s):  
Environmental Enrichment ◽  
Molecular Mechanisms ◽  
Brain Plasticity ◽  
System Development ◽  
Basic Research ◽  
Nervous System Development ◽  
Adult Brain ◽  
Aging Brain ◽  
Cerebral Neurons ◽  
And Function

Brain plasticity refers to the remarkable property of cerebral neurons to change their structure and function in response to experience, a fundamental theoretical theme in the field of basic research and a major focus for neural rehabilitation following brain disease. While much of the early work on this topic was based on deprivation approaches relying on sensory experience reduction procedures, major advances have been recently obtained using the conceptually opposite paradigm of environmental enrichment, whereby an enhanced stimulation is provided at multiple cognitive, sensory, social, and motor levels. In this survey, we aim to review past and recent work concerning the influence exerted by the environment on brain plasticity processes, with special emphasis on the underlying cellular and molecular mechanisms and starting from experimental work on animal models to move to highly relevant work performed in humans. We will initiate introducing the concept of brain plasticity and describing classic paradigmatic examples to illustrate how changes at the level of neuronal properties can ultimately affect and direct key perceptual and behavioral outputs. Then, we describe the remarkable effects elicited by early stressful conditions, maternal care, and preweaning enrichment on central nervous system development, with a separate section focusing on neurodevelopmental disorders. A specific section is dedicated to the striking ability of environmental enrichment and physical exercise to empower adult brain plasticity. Finally, we analyze in the last section the ever-increasing available knowledge on the effects elicited by enriched living conditions on physiological and pathological aging brain processes.

scholarly journals Embryonic periventricular endothelial cells demonstrate a unique pro-neurodevelopment and anti-inflammatory gene signature

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Franciele Cristina Kipper ◽  
Cleide Angolano ◽  
Ravi Vissapragada ◽  
Mauricio A. Contreras ◽  
Justin Moore ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neural Progenitor Cells ◽  
Therapeutic Potential ◽  
System Development ◽  
Gene Signature ◽  
Nervous System Development ◽  
Adult Brain ◽  
Barrier Formation ◽  
Canonical Pathways ◽  
Neurovascular Niche

AbstractBrain embryonic periventricular endothelial cells (PVEC) crosstalk with neural progenitor cells (NPC) promoting mutual proliferation, formation of tubular-like structures in the former and maintenance of stemness in the latter. To better characterize this interaction, we conducted a comparative transcriptome analysis of mouse PVEC vs. adult brain endothelial cells (ABEC) in mono-culture or NPC co-culture. We identified > 6000 differentially expressed genes (DEG), regardless of culture condition. PVEC exhibited a 30-fold greater response to NPC than ABEC (411 vs. 13 DEG). Gene Ontology (GO) analysis of DEG that were higher or lower in PVEC vs. ABEC identified “Nervous system development” and “Response to Stress” as the top significantly different biological process, respectively. Enrichment in canonical pathways included HIF1A, FGF/stemness, WNT signaling, interferon signaling and complement. Solute carriers (SLC) and ABC transporters represented an important subset of DEG, underscoring PVEC’s implication in blood–brain barrier formation and maintenance of nutrient-rich/non-toxic environment. Our work characterizes the gene signature of PVEC and their important partnership with NPC, underpinning their unique role in maintaining a healthy neurovascular niche, and in supporting brain development. This information may pave the way for additional studies to explore their therapeutic potential in neuro-degenerative diseases, such as Alzheimer’s and Parkinson’s disease.

Fibroblast growth factors as regulators of central nervous system development and function

2003 ◽  
Vol 284 (4) ◽  
pp. R867-R881 ◽  
Author(s):  
Rosanna Dono
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factors ◽  
System Development ◽  
Fibroblast Growth Factors ◽  
Brain Structures ◽  
Nervous System Development ◽  
Adult Brain ◽  
Fibroblast Growth ◽  
Fgf Signaling

Fibroblast growth factors (FGFs) are multifunctional signaling proteins that regulate developmental processes and adult physiology. Over the last few years, important progress has been made in understanding the function of FGFs in the embryonic and adult central nervous system. In this review, I will first discuss studies showing that FGF signaling is already required during formation of the neural plate. Next, I will describe how FGF signaling centers control growth and patterning of specific brain structures. Finally, I will focus on the function of FGF signaling in the adult brain and in regulating maintenance and repair of damaged neural tissues.

scholarly journals Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

PLoS Genetics ◽  
2017 ◽  
Vol 13 (1) ◽  
pp. e1006525 ◽  
Author(s):  
Cassandra R. Blanchette ◽  
Andrea Thackeray ◽  
Paola N. Perrat ◽  
Siegfried Hekimi ◽  
Claire Y. Bénard
Keyword(s):  
Nervous System ◽  
Heparan Sulfate ◽  
System Development ◽  
Nervous System Development ◽  
Functional Requirements ◽  
C Elegans
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