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https://www.readbyqxmd.com/read/28106092/pharmacological-characterisation-of-the-highly-nav1-7-selective-spider-venom-peptide-pn3a
#1
Jennifer R Deuis, Zoltan Dekan, Joshua S Wingerd, Jennifer J Smith, Nehan R Munasinghe, Rebecca F Bhola, Wendy L Imlach, Volker Herzig, David A Armstrong, K Johan Rosengren, Frank Bosmans, Stephen G Waxman, Sulayman D Dib-Hajj, Pierre Escoubas, Michael S Minett, Macdonald J Christie, Glenn F King, Paul F Alewood, Richard J Lewis, John N Wood, Irina Vetter
Human genetic studies have implicated the voltage-gated sodium channel NaV1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits NaV1.7 (IC50 0.9 nM) with at least 40-1000-fold selectivity over all other NaV subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by NaV1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28103900/gde2-is-essential-for-neuronal-survival-in-the-postnatal-mammalian-spinal-cord
#2
Clinton Cave, Sungjin Park, Marianeli Rodriguez, Mai Nakamura, Ahmet Hoke, Mikhail Pletnikov, Shanthini Sockanathan
BACKGROUND: Glycerophosphodiester phosphodiesterase 2 (GDE2) is a six-transmembrane protein that cleaves glycosylphosphatidylinositol (GPI) anchors to regulate GPI-anchored protein activity at the cell surface. In the developing spinal cord, GDE2 utilizes its enzymatic function to regulate the production of specific classes of motor neurons and interneurons; however, GDE2's roles beyond embryonic neurogenesis have yet to be defined. METHOD: Using a panel of histological, immunohistochemical, electrophysiological, behavioral, and biochemistry techniques, we characterized the postnatal Gde2 (-/-) mouse for evidence of degenerative neuropathology...
January 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28102468/mutation-of-the-herc-1-ubiquitin-ligase-impairs-associative-learning-in-the-lateral-amygdala
#3
Eva Mª Pérez-Villegas, José V Negrete-Díaz, Mª Elena Porras-García, Rocío Ruiz, Angel M Carrión, Antonio Rodríguez-Moreno, José A Armengol
Tambaleante (tbl/tbl) is a mutant mouse that carries a spontaneous Gly483Glu substitution in the HERC1 (HECT domain and RCC1 domain) E3 ubiquitin ligase protein (HERC1). The tbl/tbl mutant suffers an ataxic syndrome given the almost complete loss of cerebellar Purkinje cells during adult life. More recent analyses have identified alterations at neuromuscular junctions in these mice, as well as in other neurons of the central nervous system, such as motor neurons in the spinal cord, or pyramidal neurons in the hippocampal CA3 region and the neocortex...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28101533/experimental-design-and-data-analysis-issues-contribute-to-inconsistent-results-of-c-bouton-changes-in-amyotrophic-lateral-sclerosis
#4
S Shekar Dukkipati, Aouatef Chihi, Yiwen Wang, Sherif M Elbasiouny
The possible presence of pathological changes in cholinergic synaptic inputs [cholinergic boutons (C-boutons)] is a contentious topic within the ALS field. Conflicting data reported on this issue makes it difficult to assess the roles of these synaptic inputs in ALS. Our objective was to determine whether the reported changes are truly statistically and biologically significant and why replication is problematic. This is an urgent question, as C-boutons are an important regulator of spinal motoneuron excitability, and pathological changes in motoneuron excitability are present throughout disease progression...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28098360/morroniside-a-secoiridoid-glycoside-from-cornus-officinalis-attenuates-neuropathic-pain-by-activation-of-spinal-glucagon-like-peptide-1-receptors
#5
Meng Xu, Hai-Yun Wu, Hao Liu, Nian Gong, Yi-Rui Wang, Yong-Xiang Wang
BACKGROUND AND PURPOSE: Iridoid glycosides with intact double bond scaffold of cyclopentapyran were reversible and orthosteric agonists of glucagon-like peptide-1 (GLP-1) receptors and possess antinociception and neuroprotection. Morroniside, derived from the medicinal herb Cornus officinalis, is an atypical secoiridoid replaced by a six-membered cyclic inner ether fragment. This study investigated whether morroniside was an orthosteric GLP-1 receptor agonist and had antihypersensitivity activities in neuropathy...
January 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28089819/lentivirus-mediated-silencing-of-the-ctgf-gene-suppresses-the-formation-of-glial-scar-tissue-in-a-rat-model-of-spinal-cord-injury
#6
Yuan Wang, Qin-Jie Kong, Jing-Chuan Sun, Yong Yang, Hai-Bo Wang, Qiang Zhang, Jian-Gang Shi
BACKGROUND CONTEXT: - One of the many reactive changes following an Spinal cord injury (SCI) is the formation of a glial scar, a reactive cellular process whereby glial cells accumulate and surround central nervous system (CNS) injury sites to seal in the wound. Thus the inhibition of glial scar is of great importance for SCI recovery. PURPOSE: - This study aimed to explore the effect of lentivirus-mediated silencing of the CTGF gene on the formation of glial scar tissue in a rat model of spinal cord injury (SCI)...
January 9, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28086920/absence-of-system-xc-on-immune-cells-invading-the-central-nervous-system-alleviates-experimental-autoimmune-encephalitis
#7
Ellen Merckx, Giulia Albertini, Magdalena Paterka, Cathy Jensen, Philipp Albrecht, Michael Dietrich, Joeri Van Liefferinge, Eduard Bentea, Lise Verbruggen, Thomas Demuyser, Lauren Deneyer, Jan Lewerenz, Geert van Loo, Jacques De Keyser, Hideyo Sato, Pamela Maher, Axel Methner, Ann Massie
BACKGROUND: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System xc(-) or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration...
January 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28073938/sonic-hedgehog-guides-axons-via-zipcode-binding-protein-1-mediated-local-translation
#8
Lea Lepelletier, Sébastien D Langlois, Christopher B Kent, Kristy Welshhans, Steves Morin, Gary J Bassell, Patricia T Yam, Frédéric Charron
: Sonic hedgehog (Shh) attracts spinal cord commissural axons toward the floorplate. How Shh elicits changes in the growth cone cytoskeleton that drive growth cone turning is unknown. We find that the turning of rat commissural axons up a Shh gradient requires protein synthesis. In particular, Shh stimulation increases β-actin protein at the growth cone, even when the cell bodies have been removed. Thus Shh induces the local translation of β-actin at the growth cone. We hypothesised that this requires zipcode binding protein 1 (ZBP1), an mRNA binding protein that transports β-actin mRNA and releases it for local translation upon phosphorylation...
January 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28073086/human-neural-progenitors-derived-from-integration-free-ipscs-for-sci-therapy
#9
Ying Liu, Yiyan Zheng, Shenglan Li, Haipeng Xue, Karl Schmitt, Georgene W Hergenroeder, Jiaqian Wu, Yuanyuan Zhang, Dong H Kim, Qilin Cao
As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28072466/chronic-pain-and-impaired-glial-glutamate-transporter-function-in-lupus-prone-mice-are-ameliorated-by-blocking-csf-1-receptors
#10
Xisheng Yan, Dylan W Maixner, Fen Li, Han-Rong Weng
Systemic lupus erythematosus (SLE) is a multi-organ disease of unknown etiology in which the normal immune responses are directed against the body's own healthy tissues. Patients with SLE often suffer from chronic pain. Currently, no animal studies have been reported about the mechanisms underlying pain in SLE. In this study, the development of chronic pain in MRL lupus-prone (MRL/lpr) mice, a well-established lupus mouse model, was characterized for the first time. We found that female MRL/lpr mice developed thermal hyperalgesia at the age of 13 weeks, and mechanical allodynia at the age of 16 weeks...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28069797/oligodendrocyte-development-and-cns-myelination-are-unaffected-in-a-mouse-model-of-severe-spinal-muscular-atrophy
#11
Ryan W O'Meara, Sarah E Cummings, Yves De Repentigny, Emily McFall, John-Paul Michalski, Marc-Olivier Deguise, Sabrina Gibeault, Rashmi Kothary
The childhood neurodegenerative disease spinal muscular atrophy (SMA) is caused by loss-of-function mutations or deletions in the Survival Motor Neuron 1 (SMN1) gene resulting in insufficient levels of survival motor neuron (SMN) protein. Classically considered a motor neuron disease, increasing evidence now supports SMA as a multi-system disorder with phenotypes discovered in cortical neuron, astrocyte, and Schwann cell function within the nervous system. In this study, we sought to determine whether Smn was critical for oligodendrocyte (OL) development and central nervous system myelination...
January 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28069792/targeting-ent1-and-adenosine-tone-for-the-treatment-of-huntington-s-disease
#12
Yu-Han Kao, Meng-Syuan Lin, Chiung-Mei Chen, Yih-Ru Wu, Hui-Mei Chen, Hsing-Lin Lai, Yijuang Chern, Chun-Jung Lin
Huntington's disease (HD) is caused by an abnormal CAG expansion in the exon 1 of huntingtin gene. The treatment of HD is an unmet medical need. Given the important role of adenosine in modulating brain activity, in this study, levels of adenosine and adenine nucleotides in the cerebral spinal fluid of patients with HD and in the brain of two mouse models of HD (R6/2 and Hdh(150Q)) were analysed. The expression and activity of ENT1 in the striatum of mice with HD were measured. Targeting adenosine tone for treating HD was examined in R6/2 mice by genetic removal of ENT1 and by giving an ENT1 inhibitor, respectively...
January 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28068836/electro-acupuncture-modulates-l1-adhesion-molecule-expression-after-mouse-spinal-cord-injury
#13
Zhe Wei, Yan Wang, Weijiang Zhao, Melitta Schachner
Spinal cord injury is a devastating neurological disease in desperate need of a cure. We have previously shown that overexpression of the adhesion molecule L1 contributes to locomotor recovery after injury and were therefore interested in how electro-acupuncture would influence the expression of this molecule. Here, we investigated the effects of electro-acupuncture at "Jiaji" points (EX-B2), newly established by us, in young adult mice to determine whether improved recovery via electro-acupuncture could be due to enhanced L1 expression...
January 9, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28067393/longitudinal-assessment-of-metal-concentrations-and-copper-isotope-ratios-in-the-g93a-sod1-mouse-model-of-amyotrophic-lateral-sclerosis
#14
T Gabriel Enge, Heath Ecroyd, Dianne F Jolley, Justin J Yerbury, Anthony Dosseto
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease, which involves progressive motor neuron degeneration in the central nervous system (CNS). The G93A SOD1 mouse model simulates one of the most common causes of familial ALS through the overexpression of a mutated form of the human gene encoding copper/zinc superoxide dismutase (SOD1). Transition metals, particularly Cu and Zn, have been shown to behave abnormally in the disease context and have been hypothesized to contribute to and potentially trigger the disease...
January 9, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28063055/isolation-of-microglia-and-immune-infiltrates-from-mouse-and-primate-central-nervous-system
#15
Thais F Galatro, Ilia D Vainchtein, Nieske Brouwer, Erik W G M Boddeke, Bart J L Eggen
Microglia are the innate immune cells of the central nervous system (CNS) and play an important role in the maintenance of tissue homeostasis, providing neural support and neuroprotection. Microglia constantly survey their environment and quickly respond to homeostatic perturbations. Microglia are increasingly implicated in neuropathological and neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and glioma progression. Here, we describe a detailed isolation protocol for microglia and immune infiltrates, optimized for large amounts of post mortem tissue from human and rhesus macaque, as well as smaller tissue amounts from mouse brain and spinal cord, that yield a highly purified microglia population (up to 98 % purity)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28062667/smn-deficiency-negatively-impacts-red-pulp-macrophages-and-spleen-development-in-mouse-models-of-spinal-muscular-atrophy
#16
Marie-Therese Khairallah, Jacob Astroski, Sarah K Custer, Elliot J Androphy, Craig L Franklin, Christian L Lorson
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease that is the leading genetic cause of infantile death. It is caused by severe deficiency of the ubiquitously expressed Survival Motor Neuron (SMN) protein. SMA is characterized by α-lower motor neuron loss and muscle atrophy, however, there is a growing list of tissues impacted by SMN deficiency beyond motor neurons. The non-neuronal defects are observed in the most severe Type I SMA patients and most of the widely used SMA mouse models, however, as effective therapeutics are developed, it is unclear whether additional symptoms will be uncovered in longer lived patients...
January 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28060908/experimental-mouse-model-of-lumbar-ligamentum-flavum-hypertrophy
#17
Takeyuki Saito, Kazuya Yokota, Kazu Kobayakawa, Masamitsu Hara, Kensuke Kubota, Katsumi Harimaya, Kenichi Kawaguchi, Mitsumasa Hayashida, Yoshihiro Matsumoto, Toshio Doi, Keiichiro Shiba, Yasuharu Nakashima, Seiji Okada
Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors...
2017: PloS One
https://www.readbyqxmd.com/read/28057167/moderate-dose-regular-lifelong-alcohol-intake-changes-the-intestinal-flora-protects-against-aging-and-keeps-spatial-memory-in-the-senescence-accelerated-mouse-prone-8-samp8-model
#18
Chikako Shimizu, Yasuhiro Oki, Yutaka Mitani, Youichi Tsuchiya, Toshitaka Nabeshima
PURPOSE: Heavy and long-term alcohol consumption increase the risk of alcohol-related diseases. Epidemiological studies show moderate drinking reduces the risk of mortality, cardiovascular diseases, and brain infarction in the J-shaped or U-shaped curve effect. However, why moderate drinkers may be healthy and non-drinkers may be ill in diverse populations remains controversial. Herein, we examined the relationship between moderate/lifelong alcohol intake and aging, especially aging-related cognitive functions in senescence-accelerated mouse prone 8 (SAMP8) model...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28055860/fluorescence-diffusion-in-the-presence-of-optically-clear-tissues-in-a-mouse-head-model
#19
Daniele Ancora, Athanasios Zacharopoulos, Jorge Ripoll, Giannis Zacharakis
Diffuse Optical Tomography commonly neglects or assumes as insignificant the presence of optically clear regions in biological tissues, estimating their contribution as a small pertur-bation to light transport. The inaccuracy introduced by this prac-tice is examined in detail in the context of a complete, based on realistic geometry, virtual fluorescence Diffuse Optical Tomogra-phy experiment where a mouse head is imaged in the presence of cerebral spinal fluid. Despite the small thickness of such layer, we point out that an error is introduced when neglecting it from the model with possibly reduction in the accuracy of the reconstruc-tion and localization of the fluorescence distribution within the brain...
December 29, 2016: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/28041852/the-cellular-and-synaptic-architecture-of-the-mechanosensory-dorsal-horn
#20
Victoria E Abraira, Emily D Kuehn, Anda M Chirila, Mark W Springel, Alexis A Toliver, Amanda L Zimmerman, Lauren L Orefice, Kieran A Boyle, Ling Bai, Bryan J Song, Karleena A Bashista, Thomas G O'Neill, Justin Zhuo, Connie Tsan, Jessica Hoynoski, Michael Rutlin, Laura Kus, Vera Niederkofler, Masahiko Watanabe, Susan M Dymecki, Sacha B Nelson, Nathaniel Heintz, David I Hughes, David D Ginty
The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties...
January 12, 2017: Cell
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