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Post synaptic density

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https://www.readbyqxmd.com/read/28809922/increased-signaling-by-the-autism-related-engrailed-2-protein-enhances-dendritic-branching-and-spine-density-alters-synaptic-structural-matching-and-exaggerates-protein-synthesis
#1
Asma Soltani, Solène Lebrun, Gilles Carpentier, Giulia Zunino, Sandrine Chantepie, Auriane Maïza, Yuri Bozzi, Claire Desnos, François Darchen, Olivier Stettler
Engrailed 1 (En1) and 2 (En2) code for closely related homeoproteins acting as transcription factors and as signaling molecules that contribute to midbrain and hindbrain patterning, to development and maintenance of monoaminergic pathways, and to retinotectal wiring. En2 has been suggested to be an autism susceptibility gene and individuals with autism display an overexpression of this homeogene but the mechanisms remain unclear. We addressed in the present study the effect of exogenously added En2 on the morphology of hippocampal cells that normally express only low levels of Engrailed proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28749340/super-resolution-imaging-of-synaptic-and-extra-synaptic-ampa-receptors-with-different-sized-fluorescent-probes
#2
Sang Hak Lee, Chaoyi Jin, En Cai, Pinghua Ge, Yuji Ishitsuka, Kai Wen Teng, Andre A de Thomaz, Duncan L Nall, Murat Baday, Okunola Jeyifous, Daniel Demonte, Christopher M Dundas, Sheldon Park, Jary Y Delgado, William N Green, Paul R Selvin
Previous studies tracking AMPA receptor (AMPAR) diffusion at synapses observed a large mobile extrasynaptic AMPAR pool. Using super-resolution microscopy, we examined how fluorophore size and photostability affected AMPAR trafficking outside of, and within, post-synaptic densities (PSDs) from rats. Organic fluorescent dyes (≈4 nm), quantum dots, either small (≈10 nm diameter; sQDs) or big (>20 nm; bQDs), were coupled to AMPARs via different-sized linkers. We find that >90% of AMPARs labeled with fluorescent dyes or sQDs were diffusing in confined nanodomains in PSDs, which were stable for 15 minutes or longer...
July 27, 2017: ELife
https://www.readbyqxmd.com/read/28742076/altered-neurite-morphology-and-cholinergic-function-of-induced-pluripotent-stem-cell-derived-neurons-from-a-patient-with-kleefstra-syndrome-and-autism
#3
J Nagy, J Kobolák, S Berzsenyi, Z Ábrahám, H X Avci, I Bock, Z Bekes, B Hodoscsek, A Chandrasekaran, A Téglási, P Dezső, B Koványi, E T Vörös, L Fodor, T Szél, K Németh, A Balázs, A Dinnyés, B Lendvai, G Lévay, V Román
The aim of the present study was to establish an in vitro Kleefstra syndrome (KS) disease model using the human induced pluripotent stem cell (hiPSC) technology. Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS-ASD) carrying a deleterious premature termination codon mutation in the EHMT1 gene was identified. Patient specific hiPSCs generated from peripheral blood mononuclear cells of the KS-ASD patient were differentiated into post-mitotic cortical neurons. Lower levels of EHMT1 mRNA as well as protein expression were confirmed in these cells...
July 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28741701/dissecting-molecular-architecture-of-post-synaptic-density-at-excitatory-synapses-an-editorial-highlight-for-hierarchical-organization-and-genetically-separable-subfamilies-of-psd95-postsynaptic-supercomplexes-on-page-504
#4
EDITORIAL
Jinjun Chen, Hui-Lin Pan
This Editorial highlights a study by Frank and colleagues (2017) in the current issue of Journal of Neurochemistry. The authors report the genetic composition and stoichiometry of endogenous subfamilies of PSD95-containing supercomplexes in the mouse brain using an innovative strategy of combining gene-tagging knock-in, targeted mutations, and quantitative biochemical assays. Their findings shed new light on our understanding of the genetic hierarchy required for the assembly of distinct supercomplex subfamilies at excitatory synapses in the brain...
August 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28733898/d-cycloserine-ameliorates-autism-like-deficits-by-removing-glua2-containing-ampa-receptors-in-a-valproic-acid-induced-rat-model
#5
Han-Fang Wu, Po See Chen, Ya-Ting Hsu, Chi-Wei Lee, Tzu-Feng Wang, Yi-Ju Chen, Hui-Ching Lin
Valproic acid (VPA)-exposed rat offspring have demonstrated autism spectrum disorder (ASD) phenotypes and impaired N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala. NMDAR partial agonist D-cycloserine (DCS) has been reported to act as a cognitive enhancer by increasing the NMDAR response to improve autistic-like phenotypes in animals. However, the mechanism of DCS in alleviating the ASD is still unknown. Using combined behavioral, electrophysiological, and molecular approaches, we found that DCS administration rescued social interaction deficits and anxiety/repetitive-like behaviors observed in VPA-exposed offspring...
July 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28705167/inhibition-of-parkinsonian-tremor-with-cutaneous-afferent-evoked-by-transcutaneous-electrical-nerve-stimulation
#6
Man-Zhao Hao, Shao-Qin Xu, Zi-Xiang Hu, Fu-Liang Xu, Chuan-Xin M Niu, Qin Xiao, Ning Lan
BACKGROUND: Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. METHODS: We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS)...
July 14, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/28701928/the-hyperpolarization-activated-current-determines-synaptic-excitability-calcium-activity-and-specific-viability-of-substantia-nigra-dopaminergic-neurons
#7
Carmen Carbone, Alessia Costa, Gustavo Provensi, Guido Mannaioni, Alessio Masi
Differential vulnerability between Substantia Nigra pars compacta (SNpc) and Ventral Tegmental Area (VTA) dopaminergic (DAergic) neurons is a hallmark of Parkinson's disease (PD). Understanding the molecular bases of this key histopathological aspect would foster the development of much-needed disease-modifying therapies. Non-heterogeneous DAergic degeneration is present in both toxin-based and genetic animal models, suggesting that cellular specificity, rather than causing factors, constitutes the background for differential vulnerability...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28697947/synaptic-distribution-and-plasticity-in-primary-auditory-cortex-a1-exhibits-laminar-and-cell-specific-changes-in-the-deaf
#8
H Ruth Clemo, Stephen G Lomber, M Alex Meredith
The processing sequence through primary auditory cortex (A1) is impaired by deafness as evidenced by reduced neuronal activation in A1 of cochlear-implanted deaf cats. Such a loss of neuronal excitation should be manifest as changes in excitatory synaptic number and/or size, for which the post-synaptic correlate is the dendritic spine. Therefore, the present study sought evidence for this functional disruption using Golgi-Cox/light microscopic techniques that examined spine-bearing neurons and their dendritic spine features across all laminae in A1 of early-deaf (ototoxic lesion <1 month; raised into adulthood >16 months) and hearing cats...
July 1, 2017: Hearing Research
https://www.readbyqxmd.com/read/28688852/cdkl5-controls-postsynaptic-localization-of-glun2b-containing-nmda-receptors-in-the-hippocampus-and-regulates-seizure-susceptibility
#9
Kosuke Okuda, Shizuka Kobayashi, Masahiro Fukaya, Aya Watanabe, Takuto Murakami, Mai Hagiwara, Tempei Sato, Hiroe Ueno, Narumi Ogonuki, Sayaka Komano-Inoue, Hiroyuki Manabe, Masahiro Yamaguchi, Atsuo Ogura, Hiroshi Asahara, Hiroyuki Sakagami, Masashi Mizuguchi, Toshiya Manabe, Teruyuki Tanaka
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA...
July 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28660571/isolation-of-neuronal-synaptic-membranes-by-sucrose-gradient-centrifugation
#10
Blake R Hopiavuori, Dustin R Masser, Joseph L Wilkerson, Richard S Brush, Nawajes A Mandal, Robert E Anderson, Willard M Freeman
Sucrose gradient centrifugation is a very useful technique for isolating specific membrane types based on their size and density. This is especially useful for detecting fatty acids and lipid molecules that are targeted to specialized membranes. Without fractionation, these types of molecules could be below the levels of detection after being diluted out by the more abundant lipid molecules with a more ubiquitous distribution throughout the various cell membranes. Isolation of specific membrane types where these lipids are concentrated allows for their detection and analysis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28617434/lispro-mitigates-%C3%AE-amyloid-and-associated-pathologies-in-alzheimer-s-mice
#11
Ahsan Habib, Darrell Sawmiller, Song Li, Yang Xiang, David Rongo, Jun Tian, Huayan Hou, Jin Zeng, Adam Smith, Shengnuo Fan, Brian Giunta, Takashi Mori, Glenn Currier, Douglas Ronald Shytle, Jun Tan
Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer's disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li2CO3)...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28599322/monoamine-oxidase-a-upregulated-by-chronic-intermittent-hypoxia-activates-indoleamine-2-3-dioxygenase-and-neurodegeneration
#12
Chun-Sing Lam, Jing-Jie Li, George Lim Tipoe, Moussa B H Youdim, Man-Lung Fung
Co-morbid depression is prevalent in patients with obstructive sleep apnea. Here we report that monoamine oxidase A (MAO-A) plays pathogenic roles in the comorbidity. We found that chronic intermittent hypoxia significantly increased the MAO-A expression in the rat hippocampus and markedly decreased the dendritic length and spine density in the pyramidal neurons with less pre- and post-synaptic proteins. The MAO-A upregulation resulted in increased 5-hydroxyindoleacetic acid/serotonin ratio, oxidative stress, leading to NF-κB activation, inflammation and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28553222/dynamic-arc-sumoylation-and-selective-interaction-with-f-actin-binding-protein-drebrin-a-in-ltp-consolidation-in-vivo
#13
Rajeevkumar R Nair, Sudarshan Patil, Adrian Tiron, Tambudzai Kanhema, Debabrata Panja, Lars Schiro, Kamil Parobczak, Grzegorz Wilczynski, Clive R Bramham
Activity-regulatedcytoskeleton-associated protein (Arc) protein is implicated as a master regulator of long-term forms of synaptic plasticity and memory formation, but the mechanisms controlling Arc protein function are little known. Post-translation modification by small ubiquitin-like modifier (SUMO) proteins has emerged as a major mechanism for regulating protein-protein interactions and function. We first show in cell lines that ectopically expressed Arc undergoes mono-SUMOylation. The covalent addition of a single SUMO1 protein was confirmed by in vitro SUMOylation of immunoprecipitated Arc...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/28545543/inhibition-of-colony-stimulating-factor-1-receptor-early-in-disease-ameliorates-motor-deficits-in-sca1-mice
#14
Wenhui Qu, Andrea Johnson, Joo Hyun Kim, Abigail Lukowicz, Daniel Svedberg, Marija Cvetanovic
BACKGROUND: Polyglutamine (polyQ) expansion in the protein Ataxin-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), a fatal dominantly inherited neurodegenerative disease characterized by motor deficits, cerebellar neurodegeneration, and gliosis. Currently, there are no treatments available to delay or ameliorate SCA1. We have examined the effect of depleting microglia during the early stage of disease by using PLX, an inhibitor of colony-stimulating factor 1 receptor (CSFR1), on disease severity in a mouse model of SCA1...
May 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28539417/exposure-to-stressors-facilitates-long-term-synaptic-potentiation-in-the-lateral-habenula
#15
Hoyong Park, Jeehae Rhee, Kwanghoon Park, Jung-Soo Han, Roberto Malinow, ChiHye Chung
The lateral habenula (LHb) is a small part of the epithalamus that projects to monoamine centers in the brain. Previously, neurotransmission onto the LHb was shown to be abnormally potentiated in animal models of depression. However, synaptic plasticity in this brain area and the effect of stressor exposure on synaptic plasticity of the LHb have not been investigated. Thus, we explored whether the LHb undergoes dynamic changes in synaptic efficacy or not. First, we observed that a moderate LTP occurs in a fraction of LHb neurons obtained from naive Sprague Dawley rats...
June 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28535798/using-kalirin-conditional-knockout-mice-to-distinguish-its-role-in-dopamine-receptor-mediated-behaviors
#16
Taylor P LaRese, Yan Yan, Betty A Eipper, Richard E Mains
BACKGROUND: Mice lacking Kalirin-7 (Kal7(KO)), a Rho GDP/GTP exchange factor, self-administer cocaine at a higher rate than wildtype mice, and show an exaggerated locomotor response to experimenter-administered cocaine. Kal7, which localizes to post-synaptic densities at glutamatergic synapses, interacts directly with the GluN2B subunit of the N-methyl-D-aspartate (NMDA; GluN) receptor. Consistent with these observations, Kal7 plays an essential role in NMDA receptor dependent long term potentiation and depression, and glutamatergic transmission plays a key role in the response to chronic cocaine...
May 23, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28512860/intrinsic-cellular-and-molecular-properties-of-in-vivo-hippocampal-synaptic-plasticity-are-altered-in-the-absence-of-key-synaptic-matrix-molecules
#17
Stephan Jansen, Christine Gottschling, Andreas Faissner, Denise Manahan-Vaughan
Hippocampal synaptic plasticity comprises a key cellular mechanism for information storage. In the hippocampus, both long-term potentiation (LTP) and long-term depression (LTD) are triggered by synaptic Ca(2+) -elevations that are typically mediated by the opening of voltage-gated cation channels, such as N-methyl-d-aspartate receptors (NMDAR), in the postsynaptic density. The integrity of the post-synaptic density is ensured by the extracellular matrix (ECM). Here, we explored whether synaptic plasticity is affected in adult behaving mice that lack the ECM proteins brevican, neurocan, tenascin-C, and tenascin-R (KO)...
August 2017: Hippocampus
https://www.readbyqxmd.com/read/28473257/stress-and-corticosterone-alter-synaptic-plasticity-in-a-rat-model-of-parkinson-s-disease
#18
YongXin Hao, Aref Shabanpoor, Gerlinde A Metz
As a major influence on neuronal function and plasticity, chronic stress can affect the progression and symptoms of neurodegenerative conditions, such as Parkinson's disease (PD). Here we investigated the influence of unilateral dopamine depletion and stress on dopamine-related hallmarks of stress response and neuronal plasticity in a rat model of PD. Animals received either restraint stress or a combination of adrenalectomy and corticosterone (CORT) supplementation to clamp circulating glucocorticoid levels for three weeks prior to unilateral nigrostriatal dopamine depletion...
June 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28472657/structural-bases-of-desensitization-in-ampa-receptor-auxiliary-subunit-complexes
#19
Edward C Twomey, Maria V Yelshanskaya, Robert A Grassucci, Joachim Frank, Alexander I Sobolevsky
Fast excitatory neurotransmission is mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). AMPARs, localized at post-synaptic densities, are regulated by transmembrane auxiliary subunits that modulate AMPAR assembly, trafficking, gating, and pharmacology. Aberrancies in AMPAR-mediated signaling are associated with numerous neurological disorders. Here, we report cryo-EM structures of an AMPAR in complex with the auxiliary subunit GSG1L in the closed and desensitized states. GSG1L favors the AMPAR desensitized state, where channel closure is facilitated by profound structural rearrangements in the AMPAR extracellular domain, with ligand-binding domain dimers losing their local 2-fold rotational symmetry...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28469556/integrative-analysis-of-brain-region-specific-shank3-interactomes-for-understanding-the-heterogeneity-of-neuronal-pathophysiology-related-to-shank3-mutations
#20
Yeunkum Lee, Hyojin Kang, Bokyoung Lee, Yinhua Zhang, Yoonhee Kim, Shinhyun Kim, Won-Ki Kim, Kihoon Han
Recent molecular genetic studies have identified 100s of risk genes for various neurodevelopmental and neuropsychiatric disorders. As the number of risk genes increases, it is becoming clear that different mutations of a single gene could cause different types of disorders. One of the best examples of such a gene is SHANK3, which encodes a core scaffold protein of the neuronal excitatory post-synapse. Deletions, duplications, and point mutations of SHANK3 are associated with autism spectrum disorders, intellectual disability, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder...
2017: Frontiers in Molecular Neuroscience
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