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https://www.readbyqxmd.com/read/29779223/gene-editing-vectors-for-studying-nicotinic-acetylcholine-receptors-in-cholinergic-transmission
#1
Can Peng, Yijin Yan, Veronica J Kim, Staci E Engle, Jennifer N Berry, J Michael McIntosh, Rachael L Neve, Ryan M Drenan
Nicotinic acetylcholine receptors (nAChRs), prototype members of the cys-loop ligand gated ion channel family, are key mediators of cholinergic transmission in the central nervous system. Despite their importance, technical gaps exist in our ability to dissect the function of individual subunits in the brain. To overcome these barriers, we designed CRISPR/Cas9 small guide RNA sequences (sgRNAs) for production of loss-of-function alleles in mouse nAChR genes. These sgRNAs were validated in vitro via deep sequencing...
May 19, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29779213/differential-toxicity-of-tdp-43-isoforms-depends-on-their-sub-mitochondrial-localization-in-neuronal-cells
#2
Illari Salvatori, Alberto Ferri, Silvia Scaricamazza, Ilaria Giovannelli, Alessia Serrano, Simona Rossi, Nadia D'Ambrosi, Mauro Cozzolino, Andrea Di Giulio, Sandra Moreno, Cristiana Valle, Maria Teresa Carrì
TAR DNA binding protein 43 (TDP-43) is an RNA binding protein and a major component of protein aggregates found in Amyotrophic Lateral Sclerosis and several other neurodegenerative diseases. TDP-43 exists as a full length protein and as two shorter forms of 25 and 35 kDa. Full length mutant TDP-43s found in ALS patients re-localize from the nucleus to the cytoplasm and in part to mitochondria, where they exert a toxic role associated with neurodegeneration. However, induction of mitochondrial damage by TDP-43 fragments is yet to be clarified...
May 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29778628/environmentally-enriched-pigs-have-transcriptional-profiles-consistent-with-neuroprotective-effects-and-reduced-microglial-activity
#3
S M Brown, S J Bush, K M Summers, D A Hume, A B Lawrence
Environmental enrichment (EE) is widely used to study the effects of external factors on brain development, function and health in rodent models, but very little is known of the effects of EE on the brain in a large animal model such as the pig. Twenty-four young pigs (aged 5 weeks at start of study, 1:1 male: female ratio) were housed in environmentally enriched (EE) pens and provided with additional enrichment stimulation (a bag filled with straw) once daily. Litter, weight and sex matched controls n= (24) were housed in barren (B) conditions...
May 17, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29774215/importance-of-functional-loss-of-fus-in-ftld-als
#4
REVIEW
Shinsuke Ishigaki, Gen Sobue
Fused in sarcoma (FUS) is an RNA binding protein that regulates RNA metabolism including alternative splicing, transcription, and RNA transportation. FUS is genetically and pathologically involved in frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis (ALS). Multiple lines of evidence across diverse models suggest that functional loss of FUS can lead to neuronal dysfunction and/or neuronal cell death. Loss of FUS in the nucleus can impair alternative splicing and/or transcription, whereas dysfunction of FUS in the cytoplasm, especially in the dendritic spines of neurons, can cause mRNA destabilization...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29773756/mir126-5p-down-regulation-facilitates-axon-degeneration-and-nmj-disruption-via-a-non-cell-autonomous-mechanism-in-als
#5
Roy Maimon, Ariel Ionescu, Avichai Bonnie, Sahar Sweetat, Shane Wald-Altman, Shani Inbar, Tal Gradus, Davide Trotti, Miguel Weil, Oded Behar, Eran Perlson
Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in Amyotrophic Lateral Sclerosis (ALS) pathology. Although the disease's etiology is not fully understood, it is thought to involve a non-cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR-126-5p in pre-symptomatic ALS male mice models, and an increase in its targets: axon destabilizing type-3 Semaphorins and their co-receptor Neuropilins. Utilizing compartmentalized in vitro co-cultures, we demonstrated that myocytes expressing diverse ALS-causing mutations promote axon degeneration and NMJ dysfunction, which were inhibited by applying Neuropilin1 (NRP1) blocking antibody...
May 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29772196/ataxin-2-is-droppin-some-knowledge
#6
Lindsay A Becker, Aaron D Gitler
Ataxin-2 is an RNA-binding protein involved in translation regulation and mutated in neurodegenerative diseases, including ALS. In this issue of Neuron, Bakthavachalu et al. (2018) demonstrate that higher-order ataxin-2 RNA/protein assemblies are necessary for both translation-dependent learning and ALS-associated neurodegeneration in Drosophila.
May 16, 2018: Neuron
https://www.readbyqxmd.com/read/29767230/competing-endogenous-rna-regulatory-network-in-papillary-thyroid-carcinoma
#7
Shouhua Chen, Xiaobin Fan, He Gu, Lili Zhang, Wenhua Zhao
The present study aimed to screen all types of RNAs involved in the development of papillary thyroid carcinoma (PTC). RNA‑sequencing data of PTC and normal samples were used for screening differentially expressed (DE) microRNAs (DE‑miRNAs), long non‑coding RNAs (DE‑lncRNAs) and genes (DEGs). Subsequently, lncRNA‑miRNA, miRNA‑gene (that is, miRNA‑mRNA) and gene‑gene interaction pairs were extracted and used to construct regulatory networks. Feature genes in the miRNA‑mRNA network were identified by topological analysis and recursive feature elimination analysis...
May 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29766042/bc-rna-mislocalization-in-the-fragile-x-premutation
#8
Ilham A Muslimov, Taesun Eom, Anna Iacoangeli, Shih-Chieh Chuang, Renate K Hukema, Rob Willemsen, Dimitre G Stefanov, Robert K S Wong, Henri Tiedge
Fragile X premutation disorder is caused by CGG triplet repeat expansions in the 5' untranslated region of FMR1 mRNA. The question of how expanded CGG repeats cause disease is a subject of continuing debate. Our work indicates that CGG-repeat structures compete with regulatory BC1 RNA for access to RNA transport factor hnRNP A2. As a result, BC1 RNA is mislocalized in vivo, as its synapto-dendritic presence is severely diminished in brains of CGG-repeat knock-in animals (a premutation mouse model). Lack of BC1 RNA is known to cause seizure activity and cognitive dysfunction...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29765859/mirna-mediated-regulation-of-adult-hippocampal-neurogenesis-implications-for-epilepsy
#9
REVIEW
Pascal Bielefeld, Catherine Mooney, David C Henshall, Carlos P Fitzsimons
Hippocampal neural stem/progenitor cells (NSPCs) proliferate and differentiate to generate new neurons across the life span of most mammals, including humans. This process takes place within a characteristic local microenvironment where NSPCs interact with a variety of other cell types and encounter systemic regulatory factors. Within this microenvironment, cell intrinsic gene expression programs are modulated by cell extrinsic signals through complex interactions, in many cases involving short non-coding RNA molecules, such as miRNAs...
November 9, 2017: Brain Plasticity
https://www.readbyqxmd.com/read/29764981/mice-with-endogenous-tdp-43-mutations-exhibit-gain-of-splicing-function-and-characteristics-of-amyotrophic-lateral-sclerosis
#10
Pietro Fratta, Prasanth Sivakumar, Jack Humphrey, Kitty Lo, Thomas Ricketts, Hugo Oliveira, Jose M Brito-Armas, Bernadett Kalmar, Agnieszka Ule, Yichao Yu, Nicol Birsa, Cristian Bodo, Toby Collins, Alexander E Conicella, Alan Mejia Maza, Alessandro Marrero-Gagliardi, Michelle Stewart, Joffrey Mianne, Silvia Corrochano, Warren Emmett, Gemma Codner, Michael Groves, Ryutaro Fukumura, Yoichi Gondo, Mark Lythgoe, Erwin Pauws, Emma Peskett, Philip Stanier, Lydia Teboul, Martina Hallegger, Andrea Calvo, Adriano Chiò, Adrian M Isaacs, Nicolas L Fawzi, Eric Wang, David E Housman, Francisco Baralle, Linda Greensmith, Emanuele Buratti, Vincent Plagnol, Elizabeth Mc Fisher, Abraham Acevedo-Arozena
TDP-43 (encoded by the gene TARDBP ) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous Tardbp to dissect TDP-43 function at physiological levels both in vitro and in vivo Interestingly, we find that mutations within the C-terminal domain of TDP-43 lead to a gain of splicing function. Using two different strains, we are able to separate TDP-43 loss- and gain-of-function effects...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29763919/inhalation-of-hydrogen-of-different-concentrations-ameliorates-spinal-cord-injury-in-mice-by-protecting-spinal-cord-neurons-from-apoptosis-oxidative-injury-and-mitochondrial-structure-damages
#11
Xiao Chen, Jin Cui, Xiao Zhai, Jun Zhang, Zhengrong Gu, Xin Zhi, Weizong Weng, Panpan Pan, Liehu Cao, Fang Ji, Zhiwei Wang, Jiacan Su
BACKGROUND/AIMS: Hydrogen selectively neutralizes reactive oxygen species (ROS) and ameliorates various ROS-induced injuries. Spinal cord injury (SCI) is a serious injury to the central nervous system, and secondary SCI is closely related to excessive ROS generation. We hypothesized that hydrogen inhalation ameliorates SCI, and the mechanism of action may be related to the protective effects of hydrogen against oxidative stress, apoptosis, and mitochondrial damage. METHODS: Mechanically injured spinal cord neurons were incubated with different concentrations of hydrogen in vitro...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29761302/cftr-prevents-neuronal-apoptosis-following-cerebral-ischemia-reperfusion-via-regulating-mitochondrial-oxidative-stress
#12
Ya-Ping Zhang, Yong Zhang, Zhi-Bin Xiao, Yan-Bo Zhang, Jing Zhang, Zhi-Qiang Li, Yao-Bin Zhu
The cystic fibrosis transmembrane conductance regulator (CFTR) is linked to cell apoptosis and abundantly expressed in brain tissue. Mitochondrial oxidative stress plays a key role in activating apoptotic pathway following cerebral ischemia reperfusion (IR) injury. Reduced glutathione (GSH) is exclusively synthesized in cytosol but distributed in mitochondria. In the present study, we investigated whether CFTR affected mitochondrial oxidative stress via regulating GSH and thereby protected neurons against apoptosis following cerebral IR...
May 14, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29760717/reduced-neuronal-transcription-of-escargot-the-drosophila-gene-encoding-a-snail-type-transcription-factor-promotes-longevity
#13
Alexander V Symonenko, Natalia V Roshina, Anna V Krementsova, Elena G Pasyukova
In recent years, several genes involved in complex neuron specification networks have been shown to control life span. However, information on these genes is scattered, and studies to discover new neuronal genes and gene cascades contributing to life span control are needed, especially because of the recognized role of the nervous system in governing homeostasis, aging, and longevity. Previously, we demonstrated that several genes that encode RNA polymerase II transcription factors and that are involved in the development of the nervous system affect life span in Drosophila melanogaster ...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29760195/neuron-specific-hur-deficient-mice-spontaneously-develop-motor-neuron-disease
#14
Kevin Sun, Xiao Li, Xing Chen, Ying Bai, Gao Zhou, Olga N Kokiko-Cochran, Bruce Lamb, Thomas A Hamilton, Ching-Yi Lin, Yu-Shang Lee, Tomasz Herjan
Human Ag R (HuR) is an RNA binding protein in the ELAVL protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared with littermate control mice, indicating coordination deficiency. Using the grip-strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29757273/isolation-and-rna-extraction-of-neurons-macrophages-and-microglia-from-larval-zebrafish-brains
#15
Julie Mazzolini, Kelda Chia, Dirk Sieger
To gain a detailed understanding of the role of different CNS cells during development or the establishment and progression of brain pathologies, it is important to isolate these cells without changing their gene expression profile. The zebrafish model provides a large number of transgenic fish lines in which specific cell types are labelled; for example neurons in the NBT:DsRed line or macrophages/microglia in the mpeg1:eGFP line. Furthermore, antibodies have been developed to stain specific cells, such as microglia with the 4C4 antibody...
April 27, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29755449/immunization-elicits-antigen-specific-antibody-sequestration-in-dorsal-root-ganglia-sensory-neurons
#16
Manojkumar Gunasekaran, Prodyot K Chatterjee, Andrew Shih, Gavin H Imperato, Meghan Addorisio, Gopal Kumar, Annette Lee, John F Graf, Dan Meyer, Michael Marino, Christopher Puleo, Jeffrey Ashe, Maureen A Cox, Tak W Mak, Chad Bouton, Barbara Sherry, Betty Diamond, Ulf Andersson, Thomas R Coleman, Christine N Metz, Kevin J Tracey, Sangeeta S Chavan
The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755323/environmental-enrichment-prevents-transcriptional-disturbances-induced-by-alpha-synuclein-overexpression
#17
Zinah Wassouf, Thomas Hentrich, Sebastian Samer, Carola Rotermund, Philipp J Kahle, Ingrid Ehrlich, Olaf Riess, Nicolas Casadei, Julia M Schulze-Hentrich
Onset and progression of neurodegenerative disorders, including synucleinopathies such as Parkinson's disease, have been associated with various environmental factors. A highly compelling association from a therapeutic point of view has been found between a physically active lifestyle and a significantly reduced risk for Parkinson's disease. Mimicking such conditions in animal models by promoting physical activity, social interactions, and novel surroundings yields in a so-called enriched environment known to enhance adult neurogenesis, increase synaptic plasticity, and decelerate neuronal loss...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29754475/regulator-of-g-protein-signaling-4-rgs4-controls-morphine-reward-by-glutamate-receptor-activation-in-the-nucleus-accumbens-of-the-mouse-brain
#18
Juhwan Kim, Sueun Lee, Sohi Kang, Tae-Il Jeon, Man-Jong Kang, Tae-Hoon Lee, Yong Sik Kim, Key-Sun Kim, Heh-In Im, Changjong Moon
Crosstalk between G-protein signaling and glutamatergic transmission within the brain reward circuits is critical for long-term emotional effects (depression and anxiety), cravings, and negative withdrawal symptoms associated with opioid addiction. A previous study showed that Regulator of G-protein signaling 4 (RGS4) may be implicated in opiate action in the nucleus accumbens (NAc). However, the mechanism of the NAc-specific RGS4 actions that induce the behavioral responses to opiates remains largely unknown...
May 10, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29753879/protein-aggregation-in-cell-biology-an-aggregomics-perspective-of-health-and-disease
#19
REVIEW
Dezerae Cox, Candice Raeburn, Xiaojing Sui, Danny M Hatters
Maintaining protein homeostasis (proteostasis) is essential for cellular health and is governed by a network of quality control machinery comprising over 800 genes. When proteostasis becomes imbalanced, proteins can abnormally aggregate or become mislocalized. Inappropriate protein aggregation and proteostasis imbalance are two of the central pathological features of common neurodegenerative diseases including Alzheimer, Parkinson, Huntington, and motor neuron diseases. How aggregation contributes to the pathogenic mechanisms of disease remains incompletely understood...
May 10, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29752901/drosophila-models-of-amyotrophic-lateral-sclerosis-with-defects-in-rna-metabolism
#20
Ke Zhang, Alyssa N Coyne, Thomas E Lloyd
The fruit fly Drosophila Melanogaster has been widely used to study neurodegenerative diseases. The conservation of nervous system biology coupled with the rapid life cycle and powerful genetic tools in the fly have enabled the identification of novel therapeutic targets that have been validated in vertebrate model systems and human patients. A recent example is in the study of the devastating motor neuron degenerative disease amyotrophic lateral sclerosis (ALS). Mutations in genes that regulate RNA metabolism are a major cause of inherited ALS, and functional analysis of these genes in the fly nervous system has shed light on how mutations cause disease...
May 9, 2018: Brain Research
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