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https://www.readbyqxmd.com/read/29449802/sparc-and-glua1-containing-ampa-receptors-promote-neuronal-health-following-cns-injury
#1
Emma V Jones, Yann Bernardinelli, Juan G Zarruk, Sabrina Chierzi, Keith K Murai
The proper formation and maintenance of functional synapses in the central nervous system (CNS) requires communication between neurons and astrocytes and the ability of astrocytes to release neuromodulatory molecules. Previously, we described a novel role for the astrocyte-secreted matricellular protein SPARC (Secreted Protein, Acidic and Rich in Cysteine) in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and plasticity at developing synapses. SPARC is highly expressed by astrocytes and microglia during CNS development but its level is reduced in adulthood...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29449608/mapping-molecular-assemblies-with-fluorescence-microscopy-and-object-based-spatial-statistics
#2
Thibault Lagache, Alexandre Grassart, Stéphane Dallongeville, Orestis Faklaris, Nathalie Sauvonnet, Alexandre Dufour, Lydia Danglot, Jean-Christophe Olivo-Marin
Elucidating protein functions and molecular organisation requires to localise precisely single or aggregated molecules and analyse their spatial distributions. We develop a statistical method SODA (Statistical Object Distance Analysis) that uses either micro- or nanoscopy to significantly improve on standard co-localisation techniques. Our method considers cellular geometry and densities of molecules to provide statistical maps of isolated and associated (coupled) molecules. We use SODA with three-colour structured-illumination microscopy (SIM) images of hippocampal neurons, and statistically characterise spatial organisation of thousands of synapses...
February 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29443098/a-novel-in-vitro-live-imaging-assay-of-astrocyte-mediated-phagocytosis-using-ph-indicator-conjugated-synaptosomes
#3
Youkyeong Gloria Byun, Won-Suk Chung
Astrocytes are the major cell type in the brain and directly contact synapses and blood vessels. Although microglial cells have been considered the major immune cells and only phagocytes in the brain, recent studies have shown that astrocytes also participate in various phagocytic processes, such as developmental synapse elimination and clearance of amyloid beta plaques in Alzheimer's disease (AD). Despite these findings, the efficiency of astrocyte engulfment and degradation of their targets is unclear compared with that of microglia...
February 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29442555/direct-intertectal-inputs-are-an-integral-component-of-the-bilateral-sensorimotor-circuit-for-behavior-in-xenopus-tadpoles
#4
Abigail C Gambrill, Regina L Faulkner, Hollis T Cline
The circuit controlling visually-guided behavior in non-mammalian vertebrates, like Xenopus tadpoles, includes retinal projections to the contralateral optic tectum, where visual information is processed, and tectal motor outputs projecting ipsilaterally to hindbrain and spinal cord. Tadpoles have an intertectal commissure whose function is unknown, but it might transfer information between the tectal lobes. Differences in visual experience between the two eyes have profound effects on the development and function of visual circuits in animals with binocular vision, but the effects on animals with fully-crossed retinal projections are not clear...
February 14, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29438442/the-sirna-mediated-knockdown-of-glun3a-in-46c-derived-neural-stem-cells-affects-mrna-expression-levels-of-neural-genes-including-known-iglur-interactors
#5
Svenja Pachernegg, Sebastian Eilebrecht, Elke Eilebrecht, Hendrik Schöneborn, Sebastian Neumann, Arndt G Benecke, Michael Hollmann
For years, GluN3A was solely considered to be a dominant-negative modulator of NMDARs, since its incorporation into receptors alters hallmark features of conventional NMDARs composed of GluN1/GluN2 subunits. Only recently, increasing evidence has accumulated that GluN3A plays a more diversified role. It is considered to be critically involved in the maturation of glutamatergic synapses, and it might act as a molecular brake to prevent premature synaptic strengthening. Its expression pattern supports a putative role during neural development, since GluN3A is predominantly expressed in early pre- and postnatal stages...
2018: PloS One
https://www.readbyqxmd.com/read/29434536/heparan-sulfate-proteoglycans-as-emerging-players-in-synaptic-specificity
#6
REVIEW
Giuseppe Condomitti, Joris de Wit
Neural circuits consist of distinct neuronal cell types connected in specific patterns. The specificity of these connections is achieved in a series of sequential developmental steps that involve the targeting of neurites, the identification of synaptic partners, and the formation of specific types of synapses. Cell-surface proteins play a critical role in each of these steps. The heparan sulfate proteoglycan (HSPG) family of cell-surface proteins is emerging as a key regulator of connectivity. HSPGs are expressed throughout brain development and play important roles in axon guidance, synapse development and synapse function...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29431653/regulation-of-synapse-development-by-vgat-deletion-from-erbb4-positive-interneurons
#7
Thiri W Lin, Zhibing Tan, Arnab Barik, Dong-Min Yin, Egil Brudvik, Hongsheng Wang, Wen-Cheng Xiong, Lin Mei
GABA signaling has been implicated in neural development; however, in vivo genetic evidence is missing because mutant mice lacking GABA activity die prematurely. Here, we studied synapse development by ablating vesicular GABA transporter Vgat in in ErbB4-positive (ErbB4+) interneurons. We show that inhibitory axo-somatic synapses onto pyramidal neurons vary from one cortical layer to another; however, inhibitory synapses on axon initial segments (AISs) were similar across layers. On the other hand, PV-positive (PV+)/ErbB4+ interneurons and PV-only interneurons receive a higher number of inhibitory synapses from PV+ErbB4+ interneurons, compared with ErbB4-only interneurons...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29431645/subretinal-human-umbilical-tissue-derived-cell-transplantation-preserves-retinal-synaptic-connectivity-and-attenuates-m%C3%A3-ller-glial-reactivity
#8
Sehwon Koh, William J Chen, Nadine S Dejneka, Ian R Harris, Bin Lu, Sergey Girman, Joshua Saylor, Shaomei Wang, Cagla Eroglu
Human umbilical tissue-derived cells (hUTC or palucorcel) are currently under clinical investigation for the treatment of geographic atrophy, a late stage of macular degeneration, but how hUTC transplantation mediates vision recovery is not fully elucidated. Subretinal administration of hUTC preserves visual function in the Royal College of Surgeons (RCS) rat, a genetic model of retinal degeneration caused by Mertk loss-of-function. hUTC secrete synaptogenic and neurotrophic factors that improve the health and connectivity of the neural retina...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29428364/metaplasticity-at-the-addicted-tetrapartite-synapse-a-common-denominator-of-drug-induced-adaptations-and-potential-treatment-target-for-addiction
#9
Daniela Neuhofer, Peter Kalivas
In light of the current worldwide addiction epidemic, the need for successful therapies is more urgent than ever. Although we made substantial progress in our basic understanding of addiction, reliable therapies are lacking. Since 40-60% of patients treated for substance use disorder return to active substance use within a year following treatment discharge, alleviating the vulnerability to relapse is regarded as the most promising avenue for addiction therapy. Preclinical addiction research often focuses on maladaptive synaptic plasticity within the reward pathway...
February 8, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29427282/neonatal-exposure-to-low-dose-1-2-sevoflurane-increases-rats-hippocampal-neurogenesis-and-synaptic-plasticity-in-later-life
#10
Xi Chen, Xue Zhou, Lu Yang, Xu Miao, Di-Han Lu, Xiao-Yu Yang, Zhi-Bin Zhou, Wen-Bin Kang, Ke-Yu Chen, Li-Hua Zhou, Xia Feng
The increasing usage of general anesthetics on young children and infants has drawn extensive attention to the effects of these drugs on cognitive function later in life. Recent animal studies have revealed improvement in hippocampus-dependent performance after lower concentrations of sevoflurane exposure. However, the long-term effects of low-dose sevoflurane on the developing brain remain elusive. On postnatal day (P) 7, rats were treated with 1.2% sevoflurane (1.2% sevo group), 2.4% sevoflurane (2.4% sevo group), and air control (C group) for 6 h...
February 9, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29425353/differential-dependence-of-gabaergic-and-glutamatergic-neurons-on-glia-for-the-establishment-of-synaptic-transmission
#11
Paul Turko, Keenan Groberman, Ferdinand Browa, Stuart Cobb, Imre Vida
In the mammalian cortex, GABAergic and glutamatergic neurons represent 2 major neuronal classes, which establish inhibitory and excitatory synapses, respectively. Despite differences in their anatomy, physiology and developmental origin, both cell types require support from glial cells, particularly astrocytes, for their growth and survival. Recent experiments indicate that glutamatergic neurons also depend on astrocytes for synapse formation. However, it is not clear if the same holds true for GABAergic neurons...
February 7, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29420261/astrocyte-derived-interleukin-33-promotes-microglial-synapse-engulfment-and-neural-circuit-development
#12
Ilia D Vainchtein, Gregory Chin, Frances S Cho, Kevin W Kelley, John G Miller, Elliott C Chien, Shane A Liddelow, Phi T Nguyen, Hiromi Nakao-Inoue, Leah C Dorman, Omar Akil, Satoru Joshita, Ben A Barres, Jeanne T Paz, Ari B Molofsky, Anna V Molofsky
Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and is dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. Here, we show that the IL-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo...
February 1, 2018: Science
https://www.readbyqxmd.com/read/29415205/hdac6-is-a-therapeutic-target-in-mutant-gars-induced-charcot-marie-tooth-disease
#13
Veronick Benoy, Lawrence Van Helleputte, Robert Prior, Constantin d'Ydewalle, Wanda Haeck, Natasja Geens, Wendy Scheveneels, Begga Schevenels, M Zameel Cader, Kevin Talbot, Alan P Kozikowski, Pieter Vanden Berghe, Philip Van Damme, Wim Robberecht, Ludo Van Den Bosch
Peripheral nerve axons require a well-organized axonal microtubule network for efficient transport to ensure the constant crosstalk between soma and synapse. Mutations in more than 80 different genes cause Charcot-Marie-Tooth disease, which is the most common inherited disorder affecting peripheral nerves. This genetic heterogeneity has hampered the development of therapeutics for Charcot-Marie-Tooth disease. The aim of this study was to explore whether histone deacetylase 6 (HDAC6) can serve as a therapeutic target focusing on the mutant glycyl-tRNA synthetase (GlyRS/GARS)-induced peripheral neuropathy...
February 5, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29414352/triclosan-affects-axon-formation-in-the-neural-development-stages-of-zebrafish-embryos-danio-rerio
#14
Jin Kim, Hanseul Oh, Bokyeong Ryu, Ukjin Kim, Ji Min Lee, Cho-Rok Jung, C-Yoon Kim, Jae-Hak Park
Triclosan (TCS) is an organic compound with a wide range of antibiotic activity and has been widely used in items ranging from hygiene products to cosmetics; however, recent studies suggest that it has several adverse effects. In particular, TCS can be passed to both fetus and infants, and while some evidence suggests in vitro neurotoxicity, there are currently few studies concerning the mechanisms of TCS-induced developmental neurotoxicity. Therefore, this study aimed to clarify the effect of TCS on neural development using zebrafish models, by analyzing the morphological changes, the alterations observed in fluorescence using HuC-GFP and Olig2-dsRED transgenic zebrafish models, and neurodevelopmental gene expression...
February 2, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29413532/adolescent-pruning-and-stabilization-of-dendritic-spines-on-cortical-layer-5-pyramidal-neurons-do-not-depend-on-gonadal-hormones
#15
Josiah R Boivin, David J Piekarski, A Wren Thomas, Linda Wilbrecht
Pyramidal neurons in the neocortex receive a majority of their synapses on dendritic spines, whose growth, gain, and loss regulate the strength and identity of neural connections. Juvenile brains typically show higher spine density and turnover compared to adult brains, potentially enabling greater capacity for experience-dependent circuit 'rewiring'. Although spine pruning and stabilization in frontal cortex overlap with pubertal milestones, it is unclear if gonadal hormones drive these processes. To address this question, we used hormone manipulations and in vivo 2-photon microscopy to test for a causal relationship between pubertal hormones and spine pruning and stabilization in layer 5 neurons in the frontal cortex of female mice...
January 30, 2018: Developmental Cognitive Neuroscience
https://www.readbyqxmd.com/read/29413525/synaptotoxic-signaling-by-amyloid-beta-oligomers-in-alzheimer-s-disease-through-prion-protein-and-mglur5
#16
A Harrison Brody, Stephen M Strittmatter
Alzheimer's disease (AD) represents an impending global health crisis, yet the complexity of AD pathophysiology has so far precluded the development of any interventions to successfully slow or halt AD progression. It is clear that accumulation of Amyloid-beta (Aβ) peptide triggers progressive synapse loss to cause AD symptoms. Once initiated by Aβ, disease progression is complicated and accelerated by inflammation and by tau pathology. The recognition that Aβ peptide assumes multiple distinct states and that soluble oligomeric species (Aβo) are critical for synaptic damage is central to molecular understanding of AD...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29411505/transcriptomics-of-aged-drosophila-motor-neurons-reveals-a-matrix-metalloproteinase-that-impairs-motor-function
#17
Jorge Azpurua, Rebekah E Mahoney, Benjamin A Eaton
The neuromuscular junction (NMJ) is responsible for transforming nervous system signals into motor behavior and locomotion. In the fruit fly Drosophila melanogaster, an age-dependent decline in motor function occurs, analogous to the decline experienced in mice, humans, and other mammals. The molecular and cellular underpinnings of this decline are still poorly understood. By specifically profiling the transcriptome of Drosophila motor neurons across age using custom microarrays, we found that the expression of the matrix metalloproteinase 1 (dMMP1) gene reproducibly increased in motor neurons in an age-dependent manner...
February 7, 2018: Aging Cell
https://www.readbyqxmd.com/read/29410515/the-pka-c3-catalytic-subunit-is-required-in-two-pairs-of-interneurons-for-successful-mating-of-drosophila
#18
Marlène Cassar, Elizabeth Sunderhaus, Jill S Wentzell, Sara Kuntz, Roland Strauss, Doris Kretzschmar
Protein kinase A (PKA) has been shown to play a role in a plethora of cellular processes ranging from development to memory formation. Its activity is mediated by the catalytic subunits whereby many species express several paralogs. Drosophila encodes three catalytic subunits (PKA-C1-3) and whereas PKA-C1 has been well studied, the functions of the other two subunits were unknown. PKA-C3 is the orthologue of mammalian PRKX/Pkare and they are structurally more closely related to each other than to other catalytic subunits within their species...
February 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29409384/circular-rna-expression-alteration-in-exosomes-from-the-brain-extracellular-space-after-traumatic-brain-injury-in-mice
#19
Ruiting Zhao, Ju Zhou, Xinlong Dong, Chongwen Bi, Rongcai Jiang, Jingfei Dong, Ye Tian, Hengjie Yuan, Jian-Ning Zhang
Traumatic brain injury (TBI) has high morbidity and mortality rates. The mechanisms underlying the TBI are unclear and may include the change in biological material in exosomes. Circular RNAs (circRNAs) are enriched and stable in exosomes, which can function as microRNA (miRNA) sponges to regulate gene expression levels. Therefore, we speculated that circRNAs in exosomes might play an important role in regulating gene expression after TBI and then regulate specific signaling pathways, which may protect the brain...
February 6, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29409317/intracellular-gpcrs-play-key-roles-in-synaptic-plasticity
#20
Yuh-Jiin Ivy Jong, Steven K Harmon, Karen L O'Malley
The trillions of synaptic connections within the human brain are shaped by experience and neuronal activity both of which underlie synaptic plasticity and ultimately learning and memory. G protein-coupled receptors (GPCRs) play key roles in synaptic plasticity by strengthening or weakening synapses and/or shaping dendritic spines. While most studies of synaptic plasticity have focused on cell surface receptors and their downstream signaling partners, emerging data point to a critical new role for the very same receptors to signal from inside the cell...
February 6, 2018: ACS Chemical Neuroscience
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