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Molecular and Cellular Neurosciences

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https://www.readbyqxmd.com/read/30004015/regulation-of-actin-dynamics-during-structural-plasticity-of-dendritic-spines-signaling-messengers-and-actin-binding-proteins
#1
REVIEW
Jelena Borovac, Miquel Bosch, Kenichi Okamoto
Activity-dependent plasticity of synaptic structure and function plays an essential role in neuronal development and in cognitive functions including learning and memory. The formation, maintenance and modulation of dendritic spines are mainly controlled by the dynamics of actin filaments (F-actin) through interaction with various actin-binding proteins (ABPs) and postsynaptic signaling messengers. Induction of long-term potentiation (LTP) triggers a cascade of events involving Ca2+ signaling, intracellular pathways such as cAMP and cGMP, and regulation of ABPs such as CaMKII, Cofilin, Aip1, Arp2/3, α-actinin, Profilin and Drebrin...
July 9, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29981480/class-4-semaphorins-and-plexin-b-receptors-regulate-gabaergic-and-glutamatergic-synapse-development-in-the-mammalian-hippocampus
#2
Jacqueline E McDermott, Dena Goldblatt, Suzanne Paradis
To understand how proper circuit formation and function is established in the mammalian brain, it is necessary to define the genes and signaling pathways that instruct excitatory and inhibitory synapse development. We previously demonstrated that the ligand-receptor pair, Sema4D and Plexin-B1, regulates inhibitory synapse development on an unprecedentedly fast time-scale while having no effect on excitatory synapse development. Here, we report previously undescribed synaptogenic roles for Sema4A and Plexin-B2 and provide new insight into Sema4D and Plexin-B1 regulation of synapse development in rodent hippocampus...
July 4, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29969655/involvement-of-l-afadin-but-not-s-afadin-in-the-formation-of-puncta-adherentia-junctions-of-hippocampal-synapse
#3
Tomohiko Maruo, Shotaro Sakakibara, Muneaki Miyata, Yu Itoh, Souichi Kurita, Kenji Mandai, Takuya Sasaki, Yoshimi Takai
A hippocampal mossy fiber synapse has a complex structure in which presynaptic boutons attach to the dendritic trunk by puncta adherentia junctions (PAJs) and wrap multiply-branched spines, forming synaptic junctions. It was previously shown that afadin regulates the formation of the PAJs cooperatively with nectin-1, nectin-3, and N-cadherin. Afadin is a nectin-binding protein with two splice variants, l-afadin and s-afadin: l-afadin has an actin filament-binding domain, whereas s-afadin lacks it. It remains unknown which variant is involved in the formation of the PAJs or how afadin regulates it...
June 30, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29969654/depletion-of-astrocytic-transglutaminase-2-improves-injury-outcomes
#4
Alina Monteagudo, Julianne Feola, Heather Natola, Changyi Ji, Christoph Pröschel, Gail V W Johnson
Astrocytes play an indispensable role in maintaining a healthy, functional neural network in the central nervous system (CNS). A primary function of CNS astrocytes is to support the survival and function of neurons. In response to injury, astrocytes take on a reactive phenotype, which alters their molecular functions. Reactive astrocytes have been reported to be both beneficial and harmful to the CNS recovery process subsequent to injury. Understanding the molecular processes and regulatory proteins that determine the extent to which an astrocyte hinders or supports neuronal survival is important within the context of CNS repair...
June 30, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29953929/sex-dependent-co-occurrence-of-hypoxia-and-%C3%AE-amyloid-plaques-in-hippocampus-and-entorhinal-cortex-is-reversed-by-long-term-treatment-with-ubiquinol-and-ascorbic-acid-in-the-3-%C3%A3-tg-ad-mouse-model-of-alzheimer-s-disease
#5
Javier Frontiñan-Rubio, Francisco J Sancho-Bielsa, Juan R Peinado, Frank M LaFerla, Lydia Giménez-Llort, Mario Durán-Prado, Francisco J Alcain
Structural and functional abnormalities in the cerebral microvasculature have been observed in Alzheimer's disease (AD) patients and animal models. One cause of hypoperfusion is the thickening of the cerebrovascular basement membrane (CVBM) due to increased collagen-IV deposition around capillaries. This study investigated whether these and other alterations in the cerebrovascular system associated with AD can be prevented by long-term dietary supplementation with the antioxidant ubiquinol (Ub) stabilized with Kaneka QH P30 powder containing ascorbic acid (ASC) in a mouse model of advanced AD (3 × Tg-AD mice, 12 months old)...
June 25, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29940213/semaphorin-3a-as-an-inhibitive-factor-for-migration-of-olfactory-ensheathing-cells-through-cofilin-activation-is-involved-in-formation-of-olfactory-nerve-layer
#6
Ying Wang, Xiaomei Bao, Shiyang Wu, Xiya Shen, Fan Zhang, Zhaoting Lv, Qian Wu, Changnan Xie, Huitao Liu, Jian Lin, Honglin Teng, Zhihui Huang
Olfactory ensheathing cells (OECs) migrate from olfactory epithelium towards olfactory bulb (OB), contributing to formation of the presumptive olfactory nerve layer during development. However, it remains unclear that molecular mechanism of regulation of OEC migration in OB. In the present study, we found that OECs highly expressed the receptors of semaphorin 3A (Sema3A) in vitro and in vivo, whereas Sema3A displayed a gradient expression pattern with higher in inner layer of OB and lower in outer layer of OB...
June 22, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29936143/identification-and-characterization-of-two-novel-alternatively-spliced-e2f1-transcripts-in-the-rat-cns
#7
Dan P Jackson, Jenhao H Ting, Paul D Pozniak, Claire Meurice, Stephanie S Schleidt, Anh Dao, Amy H Lee, Eva Klinman, Kelly L Jordan-Sciutto
E2F1 is a transcription factor classically known to regulate G0 /G1 to S phase progression in the cell cycle. In addition, E2F1 also regulates a wide range of apoptotic genes and thus has been well studied in the context of neuronal death and neurodegenerative diseases. However, its function and regulation in the mature central nervous system are not well understood. Alternative splicing is a well-conserved post-transcriptional mechanism common in cells of the CNS and is necessary to generate diverse functional modifications to RNA or protein products from genes...
June 21, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29928993/urate-mitigates-oxidative-stress-and-motor-neuron-toxicity-of-astrocytes-derived-from-als-linked-sod1-g93a-mutant-mice
#8
Rachit Bakshi, Yuehang Xu, Kaly A Mueller, Xiqun Chen, Eric Granucci, Sabrina Paganoni, Ghazaleh Sadri-Vakili, Michael A Schwarzschild
Dominant mutations in an antioxidant enzyme superoxide dismutase-1 (SOD1) cause amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease characterized by loss of motor neurons. Oxidative stress has also been linked to many of the neurodegenerative diseases and is likely a central mechanism of motor neuron death in ALS. Astrocytes derived from mutant SOD1G93A mouse models or patients play a significant role in the degeneration of spinal motor neurons in ALS through a non-cell-autonomous process...
June 18, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29908232/the-association-of-spinophilin-with-disks-large-associated-protein-3-sapap3-is-regulated-by-metabotropic-glutamate-receptor-mglur-5
#9
Cameron W Morris, Darryl S Watkins, Asma B Salek, Michael C Edler, Anthony J Baucum
Spinophilin is the most abundant protein phosphatase 1 targeting protein in the postsynaptic density of dendritic spines. Spinophilin associates with myriad synaptic proteins to regulate normal synaptic communication; however, the full complement of spinophilin interacting proteins and mechanisms regulating spinophilin interactions are unclear. Here we validate an association between spinophilin and the scaffolding protein, disks large-associated protein 3 (SAP90/PSD-95 associated protein 3; SAPAP3). Loss of SAPAP3 leads to obsessive-compulsive disorder (OCD)-like behaviors due to alterations in metabotropic glutamate receptor (mGluR) signaling...
June 14, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29859891/partial-loss-of-atp13a2-causes-selective-gliosis-independent-of-robust-lipofuscinosis
#10
Sruti Rayaprolu, Yasin B Seven, John Howard, Colin Duffy, Marcelle Altshuler, Christina Moloney, Benoit I Giasson, Jada Lewis
Loss-of-function mutations in ATP13A2 are associated with three neurodegenerative diseases: a rare form of Parkinson's disease termed Kufor-Rakeb syndrome (KRS), a lysosomal storage disorder termed neuronal ceroid lipofuscinosis (NCL), and a form of hereditary spastic paraplegia (HSP). Furthermore, recent data suggests that heterozygous carriers of mutations in ATP13A2 may confer risk for the development of Parkinson's disease, similar to the association of mutations in glucocerebrosidase (GBA) with both Parkinson's disease and Gaucher's disease, a lysosomal storage disorder...
June 1, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29842943/ampa-receptor-complex-constituents-control-of-receptor-assembly-membrane-trafficking-and-subcellular-localization
#11
REVIEW
Eric Jacobi, Jakob von Engelhardt
Fast excitatory transmission at synapses of the central nervous system is mainly mediated by AMPA receptors (AMPARs). Synaptic AMPAR number and function correlates with synaptic strength. AMPARs are thus key proteins of activity-dependent plasticity in neuronal communication. Up- or down-regulation of synaptic AMPAR number is a tightly controlled dynamic process that involves export of receptors from the endoplasmic reticulum (ER) and Golgi apparatus, exocytosis and endocytosis as well as lateral diffusion of the receptors in the cell membrane...
May 26, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29802939/depressed-mitochondrial-function-and-electron-transport-complex-ii-mediated-h-2-o-2-production-in-the-cortex-of-type-1-diabetic-rodents
#12
Subir Roy Chowdhury, Jelena Djordjevic, Ella Thomson, Darrell R Smith, Benedict C Albensi, Paul Fernyhough
AIMS: Abnormalities in mitochondrial function under diabetic conditions can lead to deficits in function of cortical neurons and their support cells exhibiting a pivotal role in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. We aimed to assess mitochondrial respiration rates and membrane potential or H2 O2 generation simultaneously and expression of proteins involved in mitochondrial dynamics, ROS scavenging and AMPK/SIRT/PGC-1α pathway activity in cortex under diabetic conditions...
May 23, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29802938/differential-gene-regulatory-plasticity-between-upper-and-lower-layer-cortical-excitatory-neurons
#13
Lingling Yang, Liuzeng Chen, Chunlin Cai, Hong Li
Neocortical projection neurons consist of intracortical connected upper layer (UL, layer II-IV) neurons and subcortical connected lower layer (LL, layer V-VI) neurons. Afferent activity from the thalamus regulates layer-specific gene expression during postnatal development, which is critical for the formation of proper neocortical cytoarchitecture. Here, we show that activity-dependent gene regulation is confined to UL cortical neurons, but not LL neurons, and that this distinction is likely due to epigenetic modifications of chromatin...
May 23, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29782918/bdnf-haploinsufficiency-exerts-a-transient-and-regionally-different-influence-upon-oligodendroglial-lineage-cells-during-postnatal-development
#14
Madeline Nicholson, Rhiannon J Wood, Jessica L Fletcher, Maarten van den Buuse, Simon S Murray, Junhua Xiao
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 remains 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
#15
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
#16
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
#17
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 12, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29730177/ankyrins-roles-in-synaptic-biology-and-pathology
#18
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
#19
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 3, 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
#20
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...
June 2018: Molecular and Cellular Neurosciences
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