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synapse development

Wen-Juan Fan, Ming-Chao Yan, Lai Wang, Yi-Zheng Sun, Jin-Bo Deng, Jie-Xin Deng
Synapses are key structures in neural networks, and are involved in learning and memory in the central nervous system. Investigating synaptogenesis and synaptic aging is important in understanding neural development and neural degeneration in diseases such as Alzheimer disease and Parkinson's disease. Our previous study found that synaptogenesis and synaptic maturation were harmonized with brain development and maturation. However, synaptic damage and loss in the aging cerebellum are not well understood. This study was designed to investigate the occurrence of synaptic aging in the cerebellum by observing the ultrastructural changes of dendritic spines and synapses in cerebellar Purkinje cells of aging mice...
June 2018: Neural Regeneration Research
Julie C Savage, Katherine Picard, Fernando González-Ibáñez, Marie-Ève Tremblay
The first electron microscope was constructed in 1931. Several decades later, techniques were developed to allow the first ultrastructural analysis of microglia by transmission electron microscopy (EM). In the 50 years that followed, important roles of microglia have been identified, specifically due to the ultrastructural resolution currently available only with EM. In particular, the addition of electron-dense staining using immunohistochemical EM methods has allowed the identification of microglial cell bodies, as well as processes, which are difficult to recognize in EM, and to uncover their complex interactions with neurons and synapses...
2018: Frontiers in Immunology
Huijie Ma 马会杰, Shao-Rui Chen 陈少瑞, Hong Chen 陈红, Lingyong Li 李令勇, De-Pei Li 李德培李德培, Jing-Jing Zhou 周京京, Hui-Lin Pan 潘惠麟
Both the sympathetic nervous system and renin-angiotensin system are critically involved in hypertension development. Although angiotensin II (Ang II) stimulates hypothalamic paraventricular nucleus (PVN) neurons to increase sympathetic vasomotor tone, the molecular mechanism mediating this action remains unclear. The glutamate N -methyl- D -aspartate receptor (NMDAR) in the PVN controls sympathetic outflow in hypertension. In this study, we determined the interaction between α2δ-1 (encoded by Cacna2d1 ), commonly known as a Ca2+ channel subunit, and NMDARs in the hypothalamus and its role in Ang II-induced synaptic NMDAR activity in PVN presympathetic neurons...
June 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Cécile Baldy, Stéphanie Fournier, Samuel Boisjoly-Villeneuve, Marie-Ève Tremblay, Richard Kinkead
NEW FINDINGS: What is the central question of the study? Does neonatal stress, in the form of neonatal maternal separation, influence the maturation of microglial density, morphology, and neuronal signalling in medullary regions regulating cardio-respiratory function in rat pups? What is the main finding and its importance? Using Iba-1 immunohistochemistry, we show that neonatal maternal separation augments microglial density and the proportion of cells with an amoeboid morphology in the medulla...
June 19, 2018: Experimental Physiology
Breeanne M Soteros, Qifei Cong, Christian R Palmer, Gek-Ming Sia
The FoxP2 transcription factor and its target genes have been implicated in developmental brain diseases with a prominent language component, such as developmental verbal dyspraxia and specific language impairment. How FoxP2 affects neural circuitry development remains poorly understood. The sushi domain protein SRPX2 is a target of FoxP2, and mutations in SRPX2 are associated with language defects in humans. We have previously shown that SRPX2 is a synaptogenic protein that increases excitatory synapse density...
2018: PloS One
Anil Annamneedi, Gürsel Caliskan, Sabrina Müller, Dirk Montag, Eike Budinger, Frank Angenstein, Anna Fejtova, Wolfgang Tischmeyer, Eckart D Gundelfinger, Oliver Stork
Bassoon is a large scaffolding protein of the presynaptic active zone involved in the development of presynaptic terminals and in the regulation of neurotransmitter release at both excitatory and inhibitory brain synapses. Mice with constitutive ablation of the Bassoon (Bsn) gene display impaired presynaptic function, show sensory deficits and develop severe seizures. To specifically study the role of Bassoon at excitatory forebrain synapses and its relevance for control of behavior, we generated conditional knockout (Bsn cKO) mice by gene ablation through an Emx1 promoter-driven Cre recombinase...
June 18, 2018: Brain Structure & Function
Brian M Sweis, Erin B Larson, A David Redish, Mark J Thomas
The nucleus accumbens shell (NAcSh) is involved in reward valuation. Excitatory projections from infralimbic cortex (IL) to NAcSh undergo synaptic remodeling in rodent models of addiction and enable the extinction of disadvantageous behaviors. However, how the strength of synaptic transmission of the IL-NAcSh circuit affects decision-making information processing and reward valuation remains unknown, particularly because these processes can conflict within a given trial and particularly given recent data suggesting that decisions arise from separable information-processing algorithms...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Sivapratha Nagappan-Chettiar, Erin M Johnson-Venkatesh, Hisashi Umemori
Synapse maturation is a neural activity-dependent process during brain development, in which active synapses preferentially undergo maturation to establish efficient neural circuits in the brain. Defects in this process are implicated in various neuropsychiatric disorders. We have previously reported that a postsynaptic transmembrane protein, signal regulatory protein-α (SIRPα), plays an important role in activity-dependently directing synapse maturation. In the presence of synaptic activity, the ectodomain of SIRPα is cleaved and released and then acts as a retrograde signal to induce presynaptic maturation...
June 18, 2018: Journal of Biological Chemistry
Alberto Antonietti, Jessica Monaco, Egidio D'Angelo, Alessandra Pedrocchi, Claudia Casellato
During natural learning, synaptic plasticity is thought to evolve dynamically and redistribute within and among subcircuits. This process should emerge in plastic neural networks evolving under behavioral feedback and should involve changes distributed across multiple synaptic sites. In eyeblink classical conditioning (EBCC), the cerebellum learns to predict the precise timing between two stimuli, hence EBCC represents an elementary yet meaningful paradigm to investigate the cerebellar network functioning. We have simulated EBCC mechanisms by reconstructing a realistic cerebellar microcircuit model and embedding multiple plasticity rules imitating those revealed experimentally...
April 24, 2018: International Journal of Neural Systems
K K Frederiksen, P Kristensen, P H Honoré, G Gegelashvili, O J Bjerrum
Introduction An unmet medical need for more effective therapies of neuropathic pain exits. Here modulation of the glutaminergic system represents an unexplored possibility. Down-regulation ofglutamate transporters potentiates pain transmission by delaying the removal of glutamate from the synapse. In the spinal cord, glutamate transporter 1 (GLT-1) is responsible for more than 90% of the glutamate uptake. Ceftriaxone, a β-lactam, is believed to induce the expression of GLT-1 through the transcriptional factor (NF-ºB) pathway, which results in induced promoter activity and thereby increased synthesis of GLT-1 protein...
December 29, 2017: Scandinavian Journal of Pain
Yuanfang Guan, Tingyang Li, Hongjiu Zhang, Fan Zhu, Gilbert S Omenn
Motivation: Finding driver genes that are responsible for the aberrant proliferation rate of cancer cells is informative for both cancer research and the development of targeted drugs. The established experimental and computational methods are labor-intensive. To make algorithms feasible in real clinical settings, methods that can predict driver genes using less experimental data are urgently needed. Results: We designed an effective feature selection method and used Support Vector Machines (SVM) to predict the essentiality of the potential driver genes in cancer cell lines with only 10 genes as features...
June 15, 2018: Bioinformatics
Monika Zaręba-Kozioł, Izabela Figiel, Anna Bartkowiak-Kaczmarek, Jakub Włodarczyk
S -palmitoylation (S-PALM) is a lipid modification that involves the linkage of a fatty acid chain to cysteine residues of the substrate protein. This common posttranslational modification (PTM) is unique among other lipid modifications because of its reversibility. Hence, like phosphorylation or ubiquitination, it can act as a switch that modulates various important physiological pathways within the cell. Numerous studies revealed that S-PALM plays a crucial role in protein trafficking and function throughout the nervous system...
2018: Frontiers in Molecular Neuroscience
Ákos Kovács, Dániel Dudola, László Nyitray, Gábor Tóth, Zoltán Nagy, Zoltán Gáspári
Single alpha-helices (SAHs) are increasingly recognized as important structural and functional elements of proteins. Comprehensive identification of SAH segments in large protein datasets was largely hindered by the slow speed of the most restrictive prediction tool for their identification, FT_CHARGE on common hardware. We have previously implemented an FPGA-based version of this tool allowing fast analysis of a large number of sequences. Using this implementation, we have set up of a semi-automated pipeline capable of analyzing full UniProt releases in reasonable time and compiling monthly updates of a comprehensive database of SAH segments...
June 13, 2018: Journal of Structural Biology
Johanna Lilja, Johanna Ivaska
The formation of correct synaptic structures and neuronal connections is paramount for normal brain development and a functioning adult brain. The integrin family of cell adhesion receptors and their ligands play essential roles in the control of several processes regulating neuronal connectivity - including neurite outgrowth, the formation and maintenance of synapses, and synaptic plasticity - that are affected in neurodevelopmental disorders, such as autism spectrum disorders (ASDs) and schizophrenia. Many ASD- and schizophrenia-associated genes are linked to alterations in the genetic code of integrins and associated signalling pathways...
June 15, 2018: Journal of Cell Science
Martin W Nicholson, Aaron Sweeney, Eva Pekle, Sabina Alam, Afia B Ali, Michael Duchen, Jasmina N Jovanovic
Benzodiazepines facilitate the inhibitory actions of GABA by binding to γ-aminobutyric acid type A receptors (GABAA Rs), GABA-gated chloride/bicarbonate channels, which are the key mediators of transmission at inhibitory synapses in the brain. This activity underpins potent anxiolytic, anticonvulsant and hypnotic effects of benzodiazepines in patients. However, extended benzodiazepine treatments lead to development of tolerance, a process which, despite its important therapeutic implications, remains poorly characterised...
June 14, 2018: Molecular Psychiatry
Thomas Taetzsch, Vanessa L Brayman, Gregorio Valdez
Members of the fibroblast growth factor (FGF) family are involved in a variety of cellular processes. In the nervous system, they affect the differentiation and migration of neurons, the formation and maturation of synapses, and the repair of neuronal circuits following insults. Because of the varied yet critical functions of FGF ligands, their availability and activity must be tightly regulated for the nervous system, as well as other tissues, to properly develop and function in adulthood. In this regard, FGF binding proteins (FGFBPs) have emerged as strong candidates for modulating the actions of secreted FGFs in neural and non-neural tissues...
June 11, 2018: Biochimica et Biophysica Acta
Valerio Zerbi, Giovanna D Ielacqua, Marija Markicevic, Matthias Georg Haberl, Mark H Ellisman, Arjun A-Bhaskaran, Andreas Frick, Markus Rudin, Nicole Wenderoth
Autism spectrum disorders (ASD) are a set of complex neurodevelopmental disorders for which there is currently no targeted therapeutic approach. It is thought that alterations of genes regulating migration and synapse formation during development affect neural circuit formation and result in aberrant connectivity within distinct circuits that underlie abnormal behaviors. However, it is unknown whether deviant developmental trajectories are circuit-specific for a given autism risk-gene. We used MRI to probe changes in functional and structural connectivity from childhood to adulthood in Fragile-X (Fmr1-/y) and contactin-associated (CNTNAP2-/-) knockout mice...
July 1, 2018: Cerebral Cortex
Bouchra Edderkaoui, Liana Sargsyan, Alisa Hetrick, Hongzhe Li
Cochlear inflammatory response to various environmental insults, including acoustic and ototoxic overexposures, has been increasingly become a topic of interest. As the immune response is associated with both pathology and protection, targeting specific components of the immune response is expected to dissect the relationships between cellular damage and inflammation-associated protection and repair in the cochlea. Duffy antigen receptor for chemokines (DARC) is a member of a group of atypical chemokine receptors, and essential for chemokine-regulated leukocyte/neutrophil trafficking during inflammation...
2018: Frontiers in Molecular Neuroscience
Finetti Francesca, Cosima T Baldari
The development of T cell mediated immunity relies on the assembly of a highly specialized interface between T cell and antigen presenting cell (APC), known as the immunological synapse (IS). IS assembly is triggered when the T cell receptor (TCR) binds to specific peptide antigen presented in association to the major histocompatibility complex (MHC) by the APC, and is followed by the spatiotemporal dynamic redistribution of TCR, integrins, co-stimulatory receptors and signaling molecules, allowing for the fine-tuning and integration of the signals that lead to T cell activation...
June 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Calvin Ly, Alexandra C Greb, Lindsay P Cameron, Jonathan M Wong, Eden V Barragan, Paige C Wilson, Kyle F Burbach, Sina Soltanzadeh Zarandi, Alexander Sood, Michael R Paddy, Whitney C Duim, Megan Y Dennis, A Kimberley McAllister, Kassandra M Ori-McKenney, John A Gray, David E Olson
Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology...
June 12, 2018: Cell Reports
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