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https://www.readbyqxmd.com/read/28550169/the-gliotransmitter-d-serine-promotes-synapse-maturation-and-axonal-stabilization-in-vivo
#1
Marion R Van Horn, Arielle Strasser, Lois S Miraucourt, Loredano Pollegioni, Edward S Ruthazer
The N-methyl-D-aspartate receptor (NMDAR) is thought to play a key role in the refinement of connectivity in developing neural circuits. Pharmacological blockade or genetic loss-of-function manipulations that prevent NMDAR function during development result in the disorganization of topographic axonal projections. However, because NMDARs contribute to overall glutamatergic neurotransmission, such loss-of-function experiments fail to adequately distinguish between the roles played by NMDARs and neural activity in general...
May 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28547795/synaptogenesis-and-synaptic-protein-localization-in-the-postnatal-development-of-rod-bipolar-cell-dendrites-in-mouse-retina
#2
Zvan A Anastassov, Weiwei Wang, Felice A Dunn
Retinal responses to photons originate in rod photoreceptors and are transmitted to the ganglion cell output of the retina through the primary rod bipolar pathway. At the first synapse of this pathway, input from multiple rods is pooled into individual rod bipolar cells. This architecture is called convergence. Convergence serves to improve sensitivity of rod vision when photons are sparse. Establishment of convergence depends on the development of a proper complement of dendritic tips and transduction proteins in rod bipolar cells...
May 25, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28545760/identification-of-synaptic-pattern-of-nmda-receptor-subunits-upon-direction-selective-retinal-ganglion-cells-in-developing-and-adult-mouse-retina
#3
Jun-Seok Lee, Hang-Gu Kim, Chang-Jin Jeon
Direction selectivity of the retina is a unique mechanism and critical function of eyes for surviving. Direction-selective retinal ganglion cells (DS RGCs) strongly respond to preferred directional stimuli, but rarely respond to the opposite or null directional stimuli. These DS RGCs are sensitive to glutamate, which is secreted from bipolar cells. Using immunocytochemistry, we studied with the distributions of N-methyl-d-aspartate (NMDA) receptor subunits on the dendrites of DS RGCs in the developing and adult mouse retina...
May 22, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28542068/reduced-cortical-excitatory-synapse-number-in-apoe4-mice-is-associated-with-increased-calcineurin-activity
#4
Aidan L Neustadtl, Charisse N Winston, Maia Parsadanian, Bevan S Main, Sonia Villapol, Mark P Burns
Synaptic loss is a symptom of Alzheimer's disease (AD) that is associated with the onset of cognitive decline and the loss of executive function. The strongest genetic risk factor for AD is the APOE4 allele, which results in both a greater risk of developing AD as well as an earlier age of onset of AD. Dendritic spines, the anatomical substrate of the excitatory synapse, are reduced in the cortex of humanized APOE4 mice but the reason for this synaptic decline is unknown. Calcineurin, a calcium/calmodulin dependent phosphatase, is a mediator of dendritic spine retraction...
May 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28540658/overexpression-of-the-dyrk1a-gene-dual-specificity-tyrosine-phosphorylation-regulated-kinase-1a-induces-alterations-of-the-serotoninergic-and-dopaminergic-processing-in-murine-brain-tissues
#5
Jacqueline London, Claude Rouch, Linh Chi Bui, Elodie Assayag, Benoit Souchet, Fabrice Daubigney, Hind Medjaoui, Serge Luquet, Christophe Magnan, Jean Maurice Delabar, Julien Dairou, Nathalie Janel
Trisomy 21 (T21) or Down syndrome (DS) is the most common genetic disorder associated with intellectual disability and affects around 5 million persons worldwide. Neuroanatomical phenotypes associated with T21 include slight reduction of brain size and weight, abnormalities in several brain areas including spines dysgenesis, dendritic morphogenesis, and early neuroanatomical characteristics of Alzheimer's disease. Monoamine neurotransmitters are involved in dendrites development, functioning of synapses, memory consolidation, and their levels measured in the cerebrospinal fluid, blood, or brain areas that are modified in individuals with T21...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28539882/function-and-dysfunction-of-microglia-during-brain-development-consequences-for-synapses-and-neural-circuits
#6
REVIEW
Rosa C Paolicelli, Maria T Ferretti
Many diverse factors, ranging from stress to infections, can perturb brain homeostasis and alter the physiological activity of microglia, the immune cells of the central nervous system. Microglia play critical roles in the process of synaptic maturation and brain wiring during development. Any perturbation affecting microglial physiological function during critical developmental periods could result in defective maturation of synaptic circuits. In this review, we critically appraise the recent literature on the alterations of microglial activity induced by environmental and genetic factors occurring at pre- and early post-natal stages...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/28536440/genetic-variants-in-the-transcription-regulatory-region-of-megf10-are-associated-with-autism-in-chinese-han-population
#7
Zhiliu Wu, Jian Qin, Yang You, Yuanlin Ma, Meixiang Jia, Linyan Wang, Tianlan Lu, Weihua Yue, Yanyan Ruan, Dai Zhang, Jun Li, Lifang Wang
Multiple epidermal growth factor-like-domains 10 (MEGF10), a critical member of the apoptotic engulfment pathway, mediates axon pruning and synapse elimination during brain development. Previous studies indicated that synaptic pruning deficit was associated with autism-related phenotypes. However, the relationship between MEGF10 and autism remains poorly understood. Disease-associated variants are significantly enriched in the transcription regulatory regions. These include the transcription start site (TSS) and its cis-regulatory elements...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28528963/neuronal-activity-patterns-in-the-developing-barrel-cortex
#8
Heiko J Luhmann, Rustem Khazipov
The developing barrel cortex reveals a rich repertoire of neuronal activity patterns, which have been also found in other sensory neocortical areas and in other species including the somatosensory cortex of preterm human infants. The earliest stage is characterized by asynchronous, sparse single cell firing at low frequencies. During the second stage neurons show correlated firing, which is initially mediated by electrical synapses and subsequently transforms into network bursts depending on chemical synapses...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28524267/synaptic-activity-suppresses-expression-of-neurogenic-differentiation-factor-2-in-an-nmda-receptor-dependent-manner
#9
Fading Chen, Benjamin J Hall
Neurogenic differentiation factor 2 (NeuroD2) is a highly expressed transcription factor in the developing central nervous system. In newborn neurons, NeuroD2-mediated gene expression promotes differentiation, maturation, and survival. In addition to these early, cell-intrinsic developmental processes, NeuroD2 in post-mitotic neurons also regulates synapse growth and ion channel expression to control excitability. While NeuroD2 transactivation can be induced in an activity-dependent manner, little is known about how expression of NeuroD2 itself is regulated...
May 19, 2017: Synapse
https://www.readbyqxmd.com/read/28521702/role-of-ectonucleotidases-in-the-synapse-formation-during-brain-development-physiological-and-pathological-implications
#10
Ivana Grković, Dunja Drakulić, Jelena Martinović, Nataša Mitrović
Extracellular adenine nucleotides and nucleosides, such as ATP and adenosine, are among the most recently identified and least investigated diffusible signaling factors that contribute to the structural and functional remodeling of the brain, both during embryonic and postnatal development. Their levels in the extracellular milieu are tightly controlled by various ectonucleotidases: ectonucleotide pyrophosphatase/phosphodiesterases (E-NPP), alkaline phosphatases (AP), ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5'-nucleotidase (eN)...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28521247/cognitive-performance-of-juvenile-monkeys-after-chronic-fluoxetine-treatment
#11
Mari S Golub, Edward P Hackett, Casey E Hogrefe, Csaba Leranth, John D Elsworth, Robert H Roth
Potential long term effects on brain development are a concern when drugs are used to treat depression and anxiety in childhood. In this study, male juvenile rhesus monkeys (three-four years of age) were dosed with fluoxetine or vehicle (N=16/group) for two years. Histomorphometric examination of cortical dendritic spines conducted after euthanasia at one year postdosing (N=8/group) suggested a trend toward greater dendritic spine synapse density in prefrontal cortex of the fluoxetine-treated monkeys. During dosing, subjects were trained for automated cognitive testing, and evaluated with a test of sustained attention...
May 1, 2017: Developmental Cognitive Neuroscience
https://www.readbyqxmd.com/read/28518121/two-algorithms-for-high-throughput-and-multi-parametric-quantification-of-drosophila-neuromuscular-junction-morphology
#12
Anna Castells-Nobau, Bonnie Nijhof, Ilse Eidhof, Louis Wolf, Jolanda M Scheffer-de Gooyert, Ignacio Monedero, Laura Torroja, Jeroen A W M van der Laak, Annette Schenck
Synaptic morphology is tightly related to synaptic efficacy, and in many cases morphological synapse defects ultimately lead to synaptic malfunction. The Drosophila larval neuromuscular junction (NMJ), a well-established model for glutamatergic synapses, has been extensively studied for decades. Identification of mutations causing NMJ morphological defects revealed a repertoire of genes that regulate synapse development and function. Many of these were identified in large-scale studies that focused on qualitative approaches to detect morphological abnormalities of the Drosophila NMJ...
May 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28518055/a-positive-feedback-loop-linking-enhanced-mglur-function-and-basal-calcium-in-spinocerebellar-ataxia-type-2
#13
Pratap Meera, Stefan Pulst, Thomas Otis
Metabotropic glutamate receptor 1 (mGluR1) function in Purkinje neurons (PNs) is essential for cerebellar development and for motor learning and altered mGluR1 signaling causes ataxia. Downstream of mGluR1, dysregulation of calcium homeostasis has been hypothesized as a key pathological event in genetic forms of ataxia but the underlying mechanisms remain unclear. We find in a spinocerebellar ataxia type 2 (SCA2) mouse model that calcium homeostasis in PNs is disturbed across a broad range of physiological conditions...
May 18, 2017: ELife
https://www.readbyqxmd.com/read/28516904/lhx1-5-control-dendritogenesis-and-spine-morphogenesis-of-purkinje-cells-via-regulation-of-espin
#14
Nga Chu Lui, Wing Yip Tam, Caiji Gao, Jian-Dong Huang, Chi Chiu Wang, Liwen Jiang, Wing Ho Yung, Kin Ming Kwan
In the cerebellar cortex, Purkinje cells (PCs) receive signals from different inputs through their extensively branched dendrites and serve as an integration centre. Defects in the dendritic development of PCs thus disrupt cerebellar circuitry and cause ataxia. Here we report that specific inactivation of both Lhx1 and Lhx5 in postnatal PCs results in ataxic mutant mice with abnormal dendritic development. The PCs in the mutants have reduced expression of Espin, an F-actin cytoskeleton regulator. We show that Espin expression is transcriptionally activated by Lhx1/5...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28515914/analysis-of-the-function-of-microrna-375-in-humans-using-bioinformatics
#15
Xiaohua Chen, Baoxia Li, Rongcheng Luo, Sina Cai, Cao Zhang, Xiaolong Cao
MicroRNA-375 (miR-375) is expressed at low levels in many types of solid tumor, particularly in gastrointestinal tumors. It is considered to be important in the development of cancer and certain diseases. Thus, more detailed knowledge is required on the particular functions of miR-375. miRs function by regulating target genes. Therefore, in the current study, miRWalk (which includes the data from 10 prediction software programs) was used to predict the target genes of miR-375. The genes, which were co-predicted using five different software programs were further analyzed using Database for Annotation, Visualization and Integrated Discovery online software [including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis]...
May 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28502891/regulated-transport-of-signaling-proteins-from-synapse-to-nucleus
#16
REVIEW
Wendy A Herbst, Kelsey C Martin
Synapse-to-nucleus communication is essential for neural development, plasticity, and repair. In addition to fast electrochemical signaling, neurons employ a slower mechanism of protein transport from synapse-to-nucleus. This mechanism provides potential advantages, including the encoding of spatial information. Many synaptonuclear signaling proteins are transported from the postsynaptic compartment to the nucleus in an activity-dependent manner. The phosphorylation state of two such proteins, CRTC1 and Jacob, is dependent on the stimulus type...
May 11, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28502042/tale-of-the-good-and-the-bad-cdk5-remodeling-of-the-actin-cytoskeleton-in-the-brain
#17
REVIEW
Kavita Shah, Sandra Rossie
Cdk5 kinase, a cyclin-dependent kinase family member, is a key regulator of cytoskeletal remodeling in the brain. Cdk5 is essential for brain development during embryogenesis. After birth, it is essential for numerous neuronal processes such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity is deregulated in various brain disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemic stroke, resulting in profound remodeling of the neuronal cytoskeleton, loss of synapses, and ultimately neurodegeneration...
May 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28500055/rnai-mediated-reverse-genetic-screen-identified-drosophila-chaperones-regulating-eye-and-neuromuscular-junction-morphology
#18
Sandeep Raut, Bhagaban Mallik, Arpan Parichha, Amrutha V, Chandan Sahi, Vimlesh Kumar
Accumulation of toxic proteins in neurons have been linked with the onset of neurodegenerative diseases, which in many cases, are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and resolubilization of unfolded proteins thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance largely remains unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes...
May 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28499269/identification-of-novel-serotonin-reuptake-inhibitors-targeting-central-and-allosteric-binding-sites-a-virtual-screening-and-molecular-dynamics-simulations-study
#19
Ismail Erol, Busecan Aksoydan, Isik Kantarcioglu, Ramin E Salmas, Serdar Durdagi
The serotonin (5-hydroxytryptamine, 5HT) transporter (SERT) is a member of neurotransmitter sodium symporter (NSS) family, which maintains neurotransmitter by reuptaking 5HT into synapses. Decrease in serotonin concentrations in synaptic clefts have been reported to cause psychological and neurological disorders. Therefore, inhibition of SERT is a potent strategy for the treatment of related diseases such as depression. In this study, approximately 260,000 small molecules from an available chemical database have been virtually screened both at central and allosteric binding sites of SERT to identify potent novel candidate SERT inhibitors...
March 22, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28498949/proteolytic-cleavage-is-required-for-functional-neuroligin-2-maturation-and-trafficking-in-drosophila
#20
Renjun Tu, Jinjun Qian, Menglong Rui, Nana Tao, Mingkuan Sun, Yan Zhuang, Huihui Lv, Junhai Han, Moyi Li, Wei Xie
Neuroligins are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroligin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Neuroligins are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Neuroligin maturation and trafficking have remained largely unknown. Here, we found that Drosophila Neuroligin 2 (DNlg2) undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages...
May 11, 2017: Journal of Molecular Cell Biology
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