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Molecular and Cellular Neurosciences

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https://www.readbyqxmd.com/read/29782918/bdnf-haploinsufficiency-exerts-a-transient-and-regionally-different-influence-upon-oligodendroglial-lineage-cells-during-postnatal-development
#1
Madeline Nicholson, Rhiannon J Wood, Jessica L Fletcher, Maarten van den Buuse, Simon S Murray, Junhua Xiao
The Brain-Derived Neurotrophic Factor (BDNF) plays important roles in promoting myelination in the developing central nervous system (CNS), however the influence it exerts on oligodendrocyte development in vivo remain unclear. As BDNF knockout mice die in the perinatal period, we undertook a systematic developmental analysis of oligodendroglial lineage cells within multiple CNS regions of BDNF heterozygous (HET) mice. Our data identify that BDNF heterozygosity results in transient reductions in oligodendroglial lineage cell density and progression that are largely restricted to the optic nerve, whereas the corpus callosum, cerebral cortex, basal forebrain and spinal cord white matter tracts are unaffected...
May 18, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29777762/astrocyte-elevated-gene-1-is-a-novel-regulator-of-astrogliosis-and-excitatory-amino-acid-transporter-2-via-interplaying-with-nuclear-factor-%C3%AE%C2%BAb-signaling-in-astrocytes-from-amyotrophic-lateral-sclerosis-mouse-model-with-hsod1-g93a-mutation
#2
Xiang Yin, Shuyu Wang, Yan Qi, Xudong Wang, Hongquan Jiang, Tianhang Wang, Yueqing Yang, Ying Wang, Chunting Zhang, Honglin Feng
AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A -positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling...
May 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29777761/functional-organization-of-postsynaptic-glutamate-receptors
#3
REVIEW
Nicky Scheefhals, Harold D MacGillavry
Glutamate receptors are the most abundant excitatory neurotransmitter receptors in the brain, responsible for mediating the vast majority of excitatory transmission in neuronal networks. The AMPA- and NMDA-type ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the fast synaptic responses, while metabotropic glutamate receptors (mGluRs) are coupled to downstream signaling cascades that act on much slower timescales. These functionally distinct receptor sub-types are co-expressed at individual synapses, allowing for the precise temporal modulation of postsynaptic excitability and plasticity...
May 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29758267/the-functional-architecture-of-axonal-actin
#4
REVIEW
Marie-Jeanne Papandréou, Christophe Leterrier
The cytoskeleton builds and supports the complex architecture of neurons. It orchestrates the specification, growth, and compartmentation of the axon: axon initial segment, axonal shaft, presynapses. The cytoskeleton must then maintain this intricate architecture for the whole life of its host, but also drive its adaptation to new network demands and changing physiological conditions. Microtubules are readily visible inside axon shafts by electron microscopy, whereas axonal actin study has long been focused on dynamic structures of the axon such as growth cones...
May 11, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29738834/interaction-of-complement-system-and-microglia-activation-in-retina-and-optic-nerve-in-a-nmda-damage-model
#5
Sandra Kuehn, Sabrina Reinehr, Gesa Stute, Cara Rodust, Pia Grotegut, Alexander-Tobias Hensel, H Burkhard Dick, Stephanie C Joachim
It is known that intravitreally injected N-methyl-d-aspartate (NMDA) leads to fast retina and optic nerve degeneration and can directly activate microglia. Here, we analyzed the relevance for microglia related degenerating factors, the proteins of the complement system, at a late stage in the NMDA damage model. Therefore, different doses of NMDA (0 (PBS), 20, 40, 80 nmol) were intravitreally injected in rat eyes. Proliferative and activated microglia/macrophages (MG/Mϕ) were found in retina and optic nerve 2 weeks after NMDA injection...
May 5, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29730177/ankyrins-roles-in-synaptic-biology-and-pathology
#6
REVIEW
Katharine R Smith, Peter Penzes
Ankyrins are broadly expressed adaptors that organize diverse membrane proteins into specialized domains and link them to the sub-membranous cytoskeleton. In neurons, ankyrins are known to have essential roles in organizing the axon initial segment and nodes of Ranvier. However, recent studies have revealed novel functions for ankyrins at synapses, where they organize and stabilize neurotransmitter receptors, modulate dendritic spine morphology and control adhesion to the presynaptic site. Ankyrin genes have also been highly associated with a range of neurodevelopmental and psychiatric diseases, including bipolar disorder, schizophrenia and autism, which all demonstrate overlap in their genetics, mechanisms and phenotypes...
May 3, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29729319/autophagy-and-lysosomal-pathways-in-nervous-system-disorders
#7
REVIEW
Baris Bingol
Autophagy is an evolutionarily conserved pathway for delivering cytoplasmic cargo to lysosomes for degradation. In its classically studied form, autophagy is a stress response induced by starvation to recycle building blocks for essential cellular processes. In addition, autophagy maintains basal cellular homeostasis by degrading endogenous substrates such as cytoplasmic proteins, protein aggregates, damaged organelles, as well as exogenous substrates such as bacteria and viruses. Given their important role in homeostasis, autophagy and lysosomal machinery are genetically linked to multiple human disorders such as chronic inflammatory diseases, cardiomyopathies, cancer, and neurodegenerative diseases...
May 2, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29684457/%C3%A2-%C2%BA4-gaba-a-receptors-of-hippocampal-pyramidal-neurons-are-associated-with-resilience-against-activity-based-anorexia-for-adolescent-female-mice-but-not-for-males
#8
Yi-Wen Chen, Hannah Actor-Engel, Chiye Aoki
Activity-based anorexia (ABA) is an animal model of anorexia nervosa, a mental illness with highest mortality and with onset that is most frequently during adolescence. We questioned whether vulnerability of adolescent mice to ABA differs between sexes and whether individual differences in resilience are causally linked to alpha4betadelta-GABAA R expression. C57BL6/J WT and α4-KO adolescent male and female mice underwent ABA induction by combining wheel access with food restriction. ABA vulnerability was measured as the extent of food restriction-evoked hyperactivity on a running wheel and body weight losses...
April 20, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29678518/pattern-recognition-receptors-mediate-pro-inflammatory-effects-of-extracellular-mitochondrial-transcription-factor-a-tfam
#9
Stephanie M Schindler, Matthew G Frank, Jessica L Annis, Steven F Maier, Andis Klegeris
Neuroinflammation is a common pathogenic mechanism for a number of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Microglia, the immune cells of the brain, contribute to the onset and progression of the neuroinflammation observed in these diseases. Microglia become activated and initiate an inflammatory response by interacting with a diverse set of molecules, including the group of endogenous proteins released upon cell damage, termed damage-associated molecular patterns (DAMPs)...
April 17, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29673914/dynamics-nanoscale-organization-and-function-of-synaptic-adhesion-molecules
#10
REVIEW
Ingrid Chamma, Olivier Thoumine
Synaptic adhesion molecules not only provide a physical link between pre- and post-synaptic membranes, but also contribute to synaptic differentiation and plasticity by organizing functional elements, in particular neurotransmitter receptors. The wealth of existing adhesive protein families including many isoforms and splice variants, calls for systematic identification of the levels and exchange rates of each of those protein members at specific synapse types. Complementary to electron microscopy to identify individual synaptic contacts and biochemistry to reveal protein-protein interactions, recent super-resolution light microscopy methods combined with appropriate fluorescent labeling provide a way to measure the dynamics and sub-micron organization of selective molecular components, and their inter-relations at the synapse...
April 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29673913/epothilone-d-inhibits-microglia-mediated-spread-of-alpha-synuclein-aggregates
#11
Dario Valdinocci, Gary D Grant, Tracey C Dickson, Dean L Pountney
Multiple System Atrophy (MSA) is a progressive neurodegenerative disease characterized by chronic neuroinflammation and widespread α-synuclein (α-syn) cytoplasmic inclusions. Neuroinflammation associated with microglial cells is typically located in brain regions with α-syn deposits. The potential link between microglial cell migration and the transport of pathological α-syn protein in MSA was investigated. Qualitative analysis via immunofluorescence of MSA cases (n = 4) revealed microglial cells bearing α-syn inclusions distal from oligodendrocytes bearing α-syn cytoplasmic inclusions, as well as close interactions between microglia and oligodendrocytes bearing α-syn, suggestive of a potential transfer mechanism between microglia and α-syn bearing cells in MSA and the possibility of microglia acting as a mobile vehicle to spread α-syn between anatomically connected brain regions...
April 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29649542/new-approaches-for-solving-old-problems-in-neuronal-protein-trafficking
#12
REVIEW
Ashley M Bourke, Aaron B Bowen, Matthew J Kennedy
Fundamental cellular properties are determined by the repertoire and abundance of proteins displayed on the cell surface. As such, the trafficking mechanisms for establishing and maintaining the surface proteome must be tightly regulated for cells to respond appropriately to extracellular cues, yet plastic enough to adapt to ever-changing environments. Not only are the identity and abundance of surface proteins critical, but in many cases, their regulated spatial positioning within surface nanodomains can greatly impact their function...
April 9, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29635016/brain-microvascular-endothelial-astrocyte-cell-responses-following-japanese-encephalitis-virus-infection-in-an-in-vitro-human-blood-brain-barrier-model
#13
Adjanie Patabendige, Benedict D Michael, Alister G Craig, Tom Solomon
Japanese encephalitis virus (JEV) remains a leading cause of encephalitis, globally, which continues to grow in importance despite the availability of vaccines. Viral entry into the brain can occur via the blood-brain barrier (BBB), and inflammation at the BBB is a common final pathway in many brain infections. However, the role of the BBB during JEV infection and the contribution of the endothelial and astrocytic cell inflammation in facilitating virus entry into the brain are incompletely understood. We established a BBB model using human brain endothelial cells (HBECs) and human astrocytes...
April 7, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29631019/tetraspanins-shape-the-synapse
#14
REVIEW
Luca Murru, Edoardo Moretto, Giuseppe Martano, Maria Passafaro
Tetraspanins are a family of proteins largely expressed in mammals. These proteins share very similar structures and are involved in several biological processes spanning from the immune system to cancer growth regulation. Moreover, tetraspanins are scaffold proteins that are able to interact with each other and with a subset of proteins involved in the regulation of the central nervous system, including synapse formation, function and plasticity. In this review, we will focus on the analysis of the literature on tetraspanins, highlighting their involvement in synapse formation and function through direct or indirect modulation of synaptic proteins...
April 6, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29631018/trafficking-mechanisms-of-synaptogenic-cell-adhesion-molecules
#15
REVIEW
Luís F Ribeiro, Ben Verpoort, Joris de Wit
Nearly every aspect of neuronal function, from wiring to information processing, critically depends on the highly polarized architecture of neurons. Establishing and maintaining the distinct molecular composition of axonal and dendritic compartments requires precise control over the trafficking of the proteins that make up these cellular domains. Synaptic cell adhesion molecules (CAMs), membrane proteins with a critical role in the formation, differentiation and plasticity of synapses, require targeting to the correct pre- or postsynaptic compartment for proper functioning of neural circuits...
April 6, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29625180/a%C3%AE-oligomer-uptake-and-the-resulting-inflammatory-response-in-adult-human-astrocytes-are-precluded-by-an-anti-a%C3%AE-single-chain-variable-fragment-in-combination-with-an-apoe-mimetic-peptide
#16
Laia Montoliu-Gaya, Sandra D Mulder, Maaike A C Herrebout, Johannes C Baayen, Sandra Villegas, Robert Veerhuis
An imbalance between production and clearance of soluble amyloid-β (Aβ) initiates the pathological process in sporadic Alzheimer's disease (AD). Aβ-specific antibodies seemed promising as therapeutic option in AD mouse models. In patients, however, vascular side-effects and Aβ-antibody complex-induced microglial and/or perivascular macrophage inflammatory responses were encountered. To prevent inflammatory reactions, we designed a single chain variable fragment (scFv-h3D6), based on monoclonal antibody bapineuzumab (mAb-h3D6), but lacking the Fc region...
April 3, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29604330/metabotropic-glutamate-receptor-trafficking
#17
REVIEW
Young Ho Suh, Kai Chang, Katherine W Roche
The metabotropic glutamate receptors (mGlu receptors) are G protein-coupled receptors that bind to the excitatory neurotransmitter glutamate and are important in the modulation of neuronal excitability, synaptic transmission, and plasticity in the central nervous system. Trafficking of mGlu receptors in and out of the synaptic plasma membrane is a fundamental mechanism modulating excitatory synaptic function through regulation of receptor abundance, desensitization, and signaling profiles. In this review, we cover the regulatory mechanisms determining surface expression and endocytosis of mGlu receptors, with particular focus on post-translational modifications and receptor-protein interactions...
March 28, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29601870/anti-gm1-ganglioside-antibodies-modulate-membrane-associated-sphingomyelin-metabolism-by-altering-neutral-sphingomyelinase-activity
#18
Akihiro Ueda, Sayuri Shima, Kenitiroh Murate, Kouichi Kikuchi, Ryunosuke Nagao, Toshiki Maeda, Eri Muto, Yoshiki Niimi, Yasuaki Mizutani, Tatsuro Mutoh
Previous studies have shown that patients with Guillain-Barré syndrome express autoantibodies against ganglioside GM1 (GM1), although its pathogenic significance for the development of the disease remains to be elucidated. nSMase2 is the best characterized neutral sphingomyelinase (nSMase) found in neuronal cells. Activation of this enzyme leads to ceramide production, which is a known second messenger of the cell-death program in neuronal cells. We have explored the effects of anti-GM1 antibodies on sphingomyelin metabolism of PC12 cells stably transfected with human trk cDNA (PCtrk cells) by determining their effects on nSMase2 activity...
March 27, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29601869/d-serine-administration-affects-nitric-oxide-synthase-1-adaptor-protein-and-disc1-expression-in-sex-specific-manner
#19
Kirsten C Svane, Ericka-Kate Asis, Anton Omelchenko, Ansley J Kunnath, Linda M Brzustowicz, Steven M Silverstein, Bonnie L Firestein
Antipsychotic medications are inefficient at treating symptoms of schizophrenia (SCZ), and N-methyl d-aspartate receptor (NMDAR) agonists are potential therapeutic alternatives. As such, these agonists may act on different pathways and proteins altered in the brains of patients with SCZ than do antipsychotic medications. Here, we investigate the effects of administration of the antipsychotic haloperidol and NMDAR agonist d-serine on function and expression of three proteins that play significant roles in SCZ: nitric oxide synthase 1 adaptor protein (NOS1AP), dopamine D2 (D2) receptor, and disrupted in schizophrenia 1 (DISC1)...
March 27, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29596897/mechanisms-of-neurotrophin-trafficking-via-trk-receptors
#20
REVIEW
Emily Scott-Solomon, Rejji Kuruvilla
In neurons, long-distance communication between axon terminals and cell bodies is a critical determinant in establishing and maintaining neural circuits. Neurotrophins are soluble factors secreted by post-synaptic target tissues that retrogradely control axon and dendrite growth, survival, and synaptogenesis of innervating neurons. Neurotrophins bind Trk receptor tyrosine kinases in axon terminals to promote endocytosis of ligand-bound phosphorylated receptors into signaling endosomes. Trk-harboring endosomes function locally in axons to acutely promote growth events, and can also be retrogradely transported long-distances to remote cell bodies and dendrites to stimulate cytoplasmic and transcriptional signaling necessary for neuron survival, morphogenesis, and maturation...
March 26, 2018: Molecular and Cellular Neurosciences
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