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https://www.readbyqxmd.com/read/28723268/assay-of-calcium-transients-and-synapses-in-rat-hippocampal-neurons-by-kinetic-image-cytometry-and-high-content-analysis-an-in-vitro-model-system-for-postchemotherapy-cognitive-impairment
#1
Patrick M McDonough, Natalie L Prigozhina, Ranor C B Basa, Jeffrey H Price
Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28713243/synaptic-interactome-mining-reveals-p140cap-as-a-new-hub-for-psd-proteins-involved-in-psychiatric-and-neurological-disorders
#2
Annalisa Alfieri, Oksana Sorokina, Annie Adrait, Costanza Angelini, Isabella Russo, Alessandro Morellato, Michela Matteoli, Elisabetta Menna, Elisabetta Boeri Erba, Colin McLean, J Douglas Armstrong, Ugo Ala, Joseph D Buxbaum, Alfredo Brusco, Yohann Couté, Silvia De Rubeis, Emilia Turco, Paola Defilippi
Altered synaptic function has been associated with neurological and psychiatric conditions including intellectual disability, schizophrenia and autism spectrum disorder (ASD). Amongst the recently discovered synaptic proteins is p140Cap, an adaptor that localizes at dendritic spines and regulates their maturation and physiology. We recently showed that p140Cap knockout mice have cognitive deficits, impaired long-term potentiation (LTP) and long-term depression (LTD), and immature, filopodia-like dendritic spines...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28708060/synem-automated-synapse-detection-for-connectomics
#3
Benedikt Staffler, Manuel Berning, Kevin M Boergens, Anjali Gour, Patrick van der Smagt, Moritz Helmstaedter
Nerve tissue contains a high density of chemical synapses, about 1 per µm(3) in the mammalian cerebral cortex. Thus, even for small blocks of nerve tissue, dense connectomic mapping requires the identification of millions to billions of synapses. While the focus of connectomic data analysis has been on neurite reconstruction, synapse detection becomes limiting when datasets grow in size and dense mapping is required. Here, we report SynEM, a method for automated detection of synapses from conventionally en-bloc stained 3D electron microscopy image stacks...
July 14, 2017: ELife
https://www.readbyqxmd.com/read/28703129/precise-inhibitory-microcircuit-assembly-of-developmentally-related-neocortical-interneurons-in-clusters
#4
Xin-Jun Zhang, Zhizhong Li, Zhi Han, Khadeejah T Sultan, Kun Huang, Song-Hai Shi
GABA-ergic interneurons provide diverse inhibitions that are essential for the operation of neuronal circuits in the neocortex. However, the mechanisms that control the functional organization of neocortical interneurons remain largely unknown. Here we show that developmental origins influence fine-scale synapse formation and microcircuit assembly of neocortical interneurons. Spatially clustered neocortical interneurons originating from low-titre retrovirus-infected radial glial progenitors in the embryonic medial ganglionic eminence and preoptic area preferentially develop electrical, but not chemical, synapses with each other...
July 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28701482/analysis-of-rim-expression-and-function-at-mouse-photoreceptor-ribbon-synapses
#5
Martina Löhner, Norbert Babai, Tanja Müller, Kaspar Gierke, Jenny Atorf, Anneka Joachimsthaler, Angela Peukert, Henrik Martens, Andreas Feigenspan, Jan Kremers, Susanne Schoch, Johann Helmut Brandstätter, Hanna Regus-Leidig
RIM (RAB3A-interacting molecule) proteins are important regulators of transmitter release from active zones. At conventional chemical synapses, RIMs contribute substantially to vesicle priming and docking, and their loss reduces the readily releasable pool of synaptic vesicles by up to 75 %. The priming function of RIMs is mediated via the formation of a tripartite complex with Munc13 and RAB3A, which brings synaptic vesicles in close proximity to Ca(2+) channels and the fusion site, and activates Munc13. We reported previously that at mouse photoreceptor ribbon synapses vesicle priming is Munc13-independent...
July 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28698220/activation-of-camkiv-by-soluble-amyloid-%C3%AE-1-42-impedes-trafficking-of-axonal-vesicles-and-impairs-activity-dependent-synaptogenesis
#6
Daehun Park, Myeongsu Na, Jung Ah Kim, Unghwi Lee, Eunji Cho, Mirye Jang, Sunghoe Chang
The prefibrillar form of soluble amyloid-β (sAβ1-42) impairs synaptic function and is associated with the early phase of Alzheimer's disease (AD). We investigated how sAβ1-42 led to presynaptic defects using a quantum dot-based, single particle-tracking method to monitor synaptic vesicle (SV) trafficking along axons. We found that sAβ1-42 prevented new synapse formation induced by chemical long-term potentiation (cLTP). In cultured rat hippocampal neurons, nanomolar amounts of sAβ1-42 impaired Ca(2+) clearance from presynaptic terminals and increased the basal Ca(2+) concentration...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28696431/synaptic-activity-protects-against-ad-and-ftd-like-pathology-via-autophagic-lysosomal-degradation
#7
Y Akwa, E Gondard, A Mann, E Capetillo-Zarate, E Alberdi, C Matute, S Marty, T Vaccari, A M Lozano, E E Baulieu, D Tampellini
Changes in synaptic excitability and reduced brain metabolism are among the earliest detectable alterations associated with the development of Alzheimer's disease (AD). Stimulation of synaptic activity has been shown to be protective in models of AD beta-amyloidosis. Remarkably, deep brain stimulation (DBS) provides beneficial effects in AD patients, and represents an important therapeutic approach against AD and other forms of dementia. While several studies have explored the effect of synaptic activation on beta-amyloid, little is known about Tau protein...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28694772/connexin-dependent-neuroglial-networking-as-a-new-therapeutic-target
#8
REVIEW
Mathieu Charvériat, Christian C Naus, Luc Leybaert, Juan C Sáez, Christian Giaume
Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the "tripartite synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28694070/the-roles-of-actin-binding-domains-1-and-2-in-the-calcium-dependent-regulation-of-actin-filament-bundling-by-human-plastins
#9
Christopher L Schwebach, Richa Agrawal, Steffen Lindert, Elena Kudryashova, Dmitri S Kudryashov
The actin cytoskeleton is a complex network controlled by a vast array of intricately regulated actin binding proteins. Human plastins (PLS1, 2, and 3) are evolutionary conserved proteins that non-covalently crosslink actin filaments into tight bundles. Through stabilization of such bundles, plastins contribute, in an isoform-specific manner, to the formation of kidney and intestinal microvilli, inner ear stereocilia, immune synapses, endocytic patches, adhesion contacts, and invadosomes of immune and cancer cells...
July 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28692643/inverse-stochastic-resonance-in-networks-of-spiking-neurons
#10
Muhammet Uzuntarla, Ernest Barreto, Joaquin J Torres
Inverse Stochastic Resonance (ISR) is a phenomenon in which the average spiking rate of a neuron exhibits a minimum with respect to noise. ISR has been studied in individual neurons, but here, we investigate ISR in scale-free networks, where the average spiking rate is calculated over the neuronal population. We use Hodgkin-Huxley model neurons with channel noise (i.e., stochastic gating variable dynamics), and the network connectivity is implemented via electrical or chemical connections (i.e., gap junctions or excitatory/inhibitory synapses)...
July 10, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28684626/acetylcholinesterase-plays-a-non-neuronal-non-esterase-role-in-organogenesis
#11
Melissa A Pickett, Michael K Dush, Nanette M Nascone-Yoder
Acetylcholinesterase (AChE) is crucial for degrading acetylcholine at cholinergic synapses. In vitro studies suggest that, in addition to its role in nervous signaling, AChE can also modulate non-neuronal cell properties, although it remains controversial whether AChE functions in this capacity in vivo Here, we show that AChE plays an essential non-classical role in vertebrate gut morphogenesis. Exposure of Xenopus embryos to AChE-inhibiting chemicals results in severe defects in intestinal development. Tissue-targeted loss of function assays (via microinjection of antisense morpholino or CRISPR-Cas9) confirm that AChE is specifically required in the gut endoderm tissue, a non-neuronal cell population, where it mediates adhesion to fibronectin and regulates cell rearrangement events that drive gut lengthening and digestive epithelial morphogenesis...
July 6, 2017: Development
https://www.readbyqxmd.com/read/28654763/effect-of-tolbutamide-on-tea-induced-postsynaptic-zinc-signals-at-hippocampal-mossy-fiber-ca3-synapses
#12
Fatima Mc Bastos, Vanessa N Corceiro, Sandra A Lopes, Jose G Almeida, Carlos Manuel Margarido Matias, Jose C Dionisio, Paulo J Mendes, Fernando Ds Sampaio Dos Aidos, Rosa M Quinta-Ferreira, M Emilia Quinta-Ferreira
The application of tetraethylammonium (TEA), a blocker of voltage-dependent potassium channels, can induce long-term potentiation in the synaptic systems CA3 - CA1 and mossy fibers - CA3 pyramidal cells of the hippocampus. In the mossy fibers the depolarization evoked by extracellular TEA induces a large amount of glutamate and also of zinc release. It is considered that zinc has a neuromodulatory role at the mossy fiber synapses, which can, at least in part, be due to the activation of presynaptic ATP-dependent potassium (KATP) channels...
June 27, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28648365/direct-reprogramming-of-fibroblasts-via-a-chemically-induced-xen-like-state
#13
Xiang Li, Defang Liu, Yantao Ma, Xiaomin Du, Junzhan Jing, Lipeng Wang, Bingqing Xie, Da Sun, Shaoqiang Sun, Xueqin Jin, Xu Zhang, Ting Zhao, Jingyang Guan, Zexuan Yi, Weifeng Lai, Ping Zheng, Zhuo Huang, Yanzhong Chang, Zhen Chai, Jun Xu, Hongkui Deng
Direct lineage reprogramming, including with small molecules, has emerged as a promising approach for generating desired cell types. We recently found that during chemical induction of induced pluripotent stem cells (iPSCs) from mouse fibroblasts, cells pass through an extra-embryonic endoderm (XEN)-like state. Here, we show that these chemically induced XEN-like cells can also be induced to directly reprogram into functional neurons, bypassing the pluripotent state. The induced neurons possess neuron-specific expression profiles, form functional synapses in culture, and further mature after transplantation into the adult mouse brain...
June 20, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28618626/stochastic-lattice-model-of-synaptic-membrane-protein-domains
#14
Yiwei Li, Osman Kahraman, Christoph A Haselwandter
Neurotransmitter receptor molecules, concentrated in synaptic membrane domains along with scaffolds and other kinds of proteins, are crucial for signal transmission across chemical synapses. In common with other membrane protein domains, synaptic domains are characterized by low protein copy numbers and protein crowding, with rapid stochastic turnover of individual molecules. We study here in detail a stochastic lattice model of the receptor-scaffold reaction-diffusion dynamics at synaptic domains that was found previously to capture, at the mean-field level, the self-assembly, stability, and characteristic size of synaptic domains observed in experiments...
May 2017: Physical Review. E
https://www.readbyqxmd.com/read/28612182/invaginating-presynaptic-terminals-in-neuromuscular-junctions-photoreceptor-terminals-and-other-synapses-of-animals
#15
REVIEW
Ronald S Petralia, Ya-Xian Wang, Mark P Mattson, Pamela J Yao
Typically, presynaptic terminals form a synapse directly on the surface of postsynaptic processes such as dendrite shafts and spines. However, some presynaptic terminals invaginate-entirely or partially-into postsynaptic processes. We survey these invaginating presynaptic terminals in all animals and describe several examples from the central nervous system, including giant fiber systems in invertebrates, and cup-shaped spines, electroreceptor synapses, and some specialized auditory and vestibular nerve terminals in vertebrates...
June 13, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28612096/the-birth-of-the-synapse
#16
REVIEW
Saak V Ovsepian
It has long been held that the rise of neurons as a specialized cell type also marked the onset of the grand evolutionary journey for chemical synapses. Research over recent decades has shown, however, that the most dynamic chapters of synaptic history have been 'written' out of the context of neurobiology and neuronal evolution, dating back to the early metazoa and unicellular living forms. Here, I consider and discuss emerging evidence suggesting the exaptive origin of chemical synapses, via tinkering and neo-functionalization of already existent junctional morphologies and constituents of primeval paracrine signalling...
June 13, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28598851/mitochondrial-dysfunction-triggers-synaptic-deficits-via-activation-of-p38-map-kinase-signaling-in-differentiated-alzheimer-s-disease-trans-mitochondrial-cybrid-cells
#17
Qing Yu, Fang Du, Justin T Douglas, Haiyang Yu, Shirley ShiDu Yan, Shi Fang Yan
Loss of synapse and synaptic dysfunction contribute importantly to cognitive impairment in Alzheimer's disease (AD). Mitochondrial dysfunction and oxidative stress are early pathological features in AD-affected brain. However, the effect of AD mitochondria on synaptogenesis remains to be determined. Using human trans-mitochondrial "cybrid" (cytoplasmic hybrid) neuronal cells whose mitochondria were transferred from platelets of patients with sporadic AD or age-matched non-AD subjects with relatively normal cognition, we provide the first evidence of mitochondrial dysfunction compromises synaptic development and formation of synapse in AD cybrid cells in response to chemical-induced neuronal differentiation...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28559800/key-metabolic-enzymes-underlying-astrocytic-upregulation-of-gabaergic-plasticity
#18
Przemysław T Kaczor, Jerzy W Mozrzymas
GABAergic plasticity is recognized as a key mechanism of shaping the activity of the neuronal networks. However, its description is challenging because of numerous neuron-specific mechanisms. In particular, while essential role of glial cells in the excitatory plasticity is well established, their involvement in GABAergic plasticity only starts to emerge. To address this problem, we used two models: neuronal cell culture (NC) and astrocyte-neuronal co-culture (ANCC), where we chemically induced long-term potentiation at inhibitory synapses (iLTP)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28554401/transplantation-of-gabaergic-interneurons-for-cell-based-therapy
#19
Julien Spatazza, Walter R Mancia Leon, Arturo Alvarez-Buylla
Many neurological disorders stem from defects in or the loss of specific neurons. Neuron transplantation has tremendous clinical potential for central nervous system therapy as it may allow for the targeted replacement of those cells that are lost in diseases. Normally, most neurons are added during restricted periods of embryonic and fetal development. The permissive milieu of the developing brain promotes neuronal migration, neuronal differentiation, and synaptogenesis. Once this active period of neurogenesis ends, the chemical and physical environment of the brain changes dramatically...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552645/sculpting-neurotransmission-during-synaptic-development-by-2d-nanostructured-interfaces
#20
Niccolò Paolo Pampaloni, Denis Scaini, Fabio Perissinotto, Susanna Bosi, Maurizio Prato, Laura Ballerini
Carbon nanotube-based biomaterials critically contribute to the design of many prosthetic devices, with a particular impact in the development of bioelectronics components for novel neural interfaces. These nanomaterials combine excellent physical and chemical properties with peculiar nanostructured topography, thought to be crucial to their integration with neural tissue as long-term implants. The junction between carbon nanotubes and neural tissue can be particularly worthy of scientific attention and has been reported to significantly impact synapse construction in cultured neuronal networks...
May 25, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
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