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https://www.readbyqxmd.com/read/27919822/astrocyte-contributes-to-pain-development-via-mmp2-jnk1-2-signaling-in-a-mouse-model-of-complex-regional-pain-syndrome
#1
Guogang Tian, Xin Luo, Chaoliang Tang, Xiang Cheng, Sookja Kim Chung, Zhengyuan Xia, Chi Wai Cheung, Qulian Guo
BACKGROUND: The activation of spinal glial cells (astrocyte and microglia) is reported in patient with complex regional pain syndrome (CRPS). However, the roles of spinal glial activities in the pathophysiology of CRPS are unclear. Here, we explored the roles of spinal astrocyte and microglia and the molecular mechanisms underlying CRPS using a mouse model of chronic post-ischemia pain (CPIP). RESULTS: CPIP injury increased the level of glial fibrillary acidic protein (GFAP, reactive astrocyte biomarker), but had no significant impact on ionized calcium binding adaptor molecule 1 (IBA1, reactive microglia biomarker), in the ipsilateral dorsal horn on post-injury day (PID) 3 when the pain threshold started to reduce significantly...
December 2, 2016: Life Sciences
https://www.readbyqxmd.com/read/27916453/shank3-deficiency-impairs-heat-hyperalgesia-and-trpv1-signaling-in-primary-sensory-neurons
#2
Qingjian Han, Yong Ho Kim, Xiaoming Wang, Di Liu, Zhi-Jun Zhang, Alexandra L Bey, Mark Lay, Wonseok Chang, Temugin Berta, Yan Zhang, Yong-Hui Jiang, Ru-Rong Ji
Abnormal pain sensitivity is commonly associated with autism spectrum disorders (ASDs) and affects the life quality of ASD individuals. SHANK3 deficiency was implicated in ASD and pain dysregulation. Here, we report functional expression of SHANK3 in mouse dorsal root ganglion (DRG) sensory neurons and spinal cord presynaptic terminals. Homozygous and heterozygous Shank3 complete knockout (Δe4-22) results in impaired heat hyperalgesia in inflammatory and neuropathic pain. Specific deletion of Shank3 in Nav1...
November 24, 2016: Neuron
https://www.readbyqxmd.com/read/27912911/hesperidin-ameliorates-immunological-outcome-and-reduces-neuroinflammation-in-the-mouse-model-of-multiple-sclerosis
#3
Dariush Haghmorad, Mohammad Bagher Mahmoudi, Zohreh Salehipour, Zoleikha Jalayer, Amir Abbas Momtazi Brojeni, Maryam Rastin, Parviz Kokhaei, Mahmoud Mahmoudi
Multiple sclerosis (MS) is the most abundant central nervous system (CNS) inflammatory disease, which is due to the reaction of auto reactive T cells with own myelin proteins, leading to physical disorder and paralysis among people suffering the disease. Hesperidin, a flavanone glycoside found abundantly in citrus fruits possesses a wide range of pharmacological properties including potential anti-inflammatory and anti-cancer effects. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of hesperidin on MS alleviation...
November 26, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27911395/preparation-of-primary-mixed-glial-cultures-from-adult-mouse-spinal-cord-tissue
#4
Jennifer T Malon, Ling Cao
It has been well-accepted that spinal cord glial responses contribute significantly to the development of neuropathic pain. Tremendous information regarding glial activities at the cellular and molecular levels has been obtained through in vitro cell culture systems. The in vitro systems utilized, mainly include primary glia derived from neonatal brain cortical tissue and immortalized cell lines. However, these systems may not reflect the characteristics of spinal cord glial cells in vivo. In order to further investigate the roles of spinal cord glial cells in the development of peripheral nerve injury-induced neuropathic pain using a culture system that better reflects the in vivo condition, our laboratory has developed a method to establish primary spinal cord mixed glial cultures from adult mice...
November 19, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911337/effect-of-the-butyrate-prodrug-pivaloyloxymethyl-butyrate-an9-on-a-mouse-model-for-spinal-muscular-atrophy
#5
Jonathan D Edwards, Matthew E R Butchbach
Spinal muscular atrophy (SMA) is an early-onset motor neuron disease that leads to loss of muscle function. Butyrate (BA)-based compounds markedly improve the survival and motor phenotype of SMA mice. In this study, we examine the protective effects of the BA prodrug pivaloyloxymethyl butyrate (AN9) on the survival of SMNΔ7 SMA mice. Oral administration of AN9 beginning at PND04 almost doubled the average lifespan of SMNΔ7 SMA mice. AN9 treatment also increased the growth rate of SMNΔ7 SMA mice when compared to vehicle-treated SMNΔ7 SMA mice...
November 29, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27907033/normalization-of-patient-identified-plasma-biomarkers-in-smn%C3%AE-7-mice-following-postnatal-smn-restoration
#6
W David Arnold, Sandra Duque, Chitra C Iyer, Phillip Zaworski, Vicki L McGovern, Shannon J Taylor, Katharine M von Herrmann, Dione T Kobayashi, Karen S Chen, Stephen J Kolb, Sergey V Paushkin, Arthur H M Burghes
INTRODUCTION AND OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA is caused by homozygous loss of the SMN1 gene and retention of the SMN2 gene resulting in reduced levels of full length SMN protein that are insufficient for motor neuron function. Various treatments that restore levels of SMN are currently in clinical trials and biomarkers are needed to determine the response to treatment. Here, we sought to investigate in SMA mice a set of plasma analytes, previously identified in patients with SMA to correlate with motor function...
2016: PloS One
https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#7
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27902570/preprotachykinin-a-ppta-is-expressed-by-a-distinct-population-of-excitatory-neurons-in-the-mouse-superficial-spinal-dorsal-horn-including-cells-that-respond-to-noxious-and-pruritic-stimuli
#8
Maria Gutierrez-Mecinas, Andrew M Bell, Alina Marin, Rebecca Taylor, Kieran A Boyle, Takahiro Furuta, Masahiko Watanabe, Erika Polgár, Andrew J Todd
The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined three non-overlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B (NKB) and gastrin-releasing peptide (GRP). Here we identify and characterise another population: neurons that express the tachykinin peptide substance P...
November 25, 2016: Pain
https://www.readbyqxmd.com/read/27891608/compensatory-axon-sprouting-for-very-slow-axonal-die-back-in-a-transgenic-model-of-spinal-muscular-atrophy-type-iii
#9
Esther Udina, Charles Putman, Luke Harris, N Tyreman, Victoria Cook, Tessa Gordon
Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn+/- transgenic mouse model of mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections...
November 28, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27890794/target-regulation-of-pi3k-akt-mtor-pathway-by-cannabidiol-in-treatment-of-experimental-multiple-sclerosis
#10
Sabrina Giacoppo, Federica Pollastro, Gianpaolo Grassi, Placido Bramanti, Emanuela Mazzon
This study was aimed to investigate whether treatment with purified cannabidiol (CBD) may counteract the development of experimental multiple sclerosis (MS), by targeting the PI3K/Akt/mTOR pathway. Although the PI3K/Akt/mTOR pathway was found to be activated by cannabinoids in several immune and non-immune cells, currently, there is no data about the effects of CBD in the PI3K/Akt/mTOR activity in MS. Experimental Autoimmune Encephalomyelitis (EAE), the most common model of MS, was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55...
November 25, 2016: Fitoterapia
https://www.readbyqxmd.com/read/27889959/fumaric-acid-esters-attenuate-secondary-degeneration-following-spinal-cord-injury
#11
Marika Cordaro, Giovanna Casili, Irene Paterniti, Salvatore Cuzzocrea, Emanuela Esposito
Spinal cord injury (SCI) causes permanent changes in motor, sensory and autonomic functions. Unfortunately, there are not a stable cures and current treatments include surgical decompression, methylprednisolone and hemodynamic control that lead to modest function recovery. Fumaric acid esters (FAEs) were firstly used in the management of an immunological skin disorder, such as psoriasis. Because of their potent anti-inflammatory effects, they have been introduced in multiple sclerosis. Investigation shown not only anti-inflammatory, but also supposed neuroprotective mechanism of action...
November 27, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27882348/humanized-neuronal-chimeric-mouse-brain-generated-by-neonatally-engrafted-human-ipsc-derived-primitive-neural-progenitor-cells
#12
Chen Chen, Woo-Yang Kim, Peng Jiang
The creation of a humanized chimeric mouse nervous system permits the study of human neural development and disease pathogenesis using human cells in vivo. Humanized glial chimeric mice with the brain and spinal cord being colonized by human glial cells have been successfully generated. However, generation of humanized chimeric mouse brains repopulated by human neurons to possess a high degree of chimerism have not been well studied. Here we created humanized neuronal chimeric mouse brains by neonatally engrafting the distinct and highly neurogenic human induced pluripotent stem cell (hiPSC)-derived rosette-type primitive neural progenitors...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27882347/ml372-blocks-smn-ubiquitination-and-improves-spinal-muscular-atrophy-pathology-in-mice
#13
Mahlet B Abera, Jingbo Xiao, Jonathan Nofziger, Steve Titus, Noel Southall, Wei Zheng, Kasey E Moritz, Marc Ferrer, Jonathan J Cherry, Elliot J Androphy, Amy Wang, Xin Xu, Christopher Austin, Kenneth H Fischbeck, Juan J Marugan, Barrington G Burnett
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease and one of the leading inherited causes of infant mortality. SMA results from insufficient levels of the survival motor neuron (SMN) protein, and studies in animal models of the disease have shown that increasing SMN protein levels ameliorates the disease phenotype. Our group previously identified and optimized a new series of small molecules, with good potency and toxicity profiles and reasonable pharmacokinetics, that were able to increase SMN protein levels in SMA patient-derived cells...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27881777/temporal-profiling-of-astrocyte-precursors-reveals-parallel-roles-for-asef-during-development-and-after-injury
#14
Lesley S Chaboub, Jeanne M Manalo, Hyun Kyoung Lee, Stacey M Glasgow, Fengju Chen, Yoshihiro Kawasaki, Tetsu Akiyama, Chay T Kuo, Chad J Creighton, Carrie A Mohila, Benjamin Deneen
: Lineage development is a stepwise process, governed by stage-specific regulatory factors and associated markers. Astrocytes are one of the principle cell types in the CNS and the stages associated with their development remain very poorly defined. To identify these stages, we performed gene-expression profiling on astrocyte precursor populations in the spinal cord, identifying distinct patterns of gene induction during their development that are strongly correlated with human astrocytes...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27880068/human-hair-follicle-associated-pluripotent-hhap-stem-cells-differentiate-to-cardiac-muscle-cells
#15
Natsuko Tohgi, Koya Obara, Masateru Yashiro, Yuko Hamada, Nobuko Arakawa, Sumiyuki Mii, Ryoichi Aki, Robert M Hoffman, Yasuyuki Amoh
We have previously demonstrated that the nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells are located in the bulge area. HAP stem cells have been previously shown to differentiate to neurons, glial cells, keratinocytes, smooth-muscle cells, melanocytes and cardiac-muscle cells in vitro. Subsequently, we demonstrated that HAP stem cells could effect nerve and spinal cord regeneration in mouse models, differentiating to Schwann cells and neurons. In previous studies, we established an efficient protocol for the differentiation of cardiac-muscle cells from mouse HAP stem cells...
November 23, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27870893/activin-receptor-type-iib-inhibition-improves-muscle-phenotype-and-function-in-a-mouse-model-of-spinal-muscular-atrophy
#16
Min Liu, David W Hammers, Elisabeth R Barton, H Lee Sweeney
Spinal muscular atrophy (SMA) is a devastating neurodegenerative disorder that causes progressive muscle atrophy and weakness. Using adeno-associated virus-mediated gene transfer, we evaluated the potential to improve skeletal muscle weakness via systemic, postnatal inhibition of either myostatin or all signaling via the activin receptor type IIB (ActRIIB). After demonstrating elevated p-SMAD3 content and differential content of ActRIIB ligands, 4-week-old male C/C SMA model mice were treated intraperitoneally with 1x1012 genome copies of pseudotype 2/8 virus encoding a soluble form of the ActRIIB extracellular domain (sActRIIB) or protease-resistant myostatin propeptide (dnMstn) driven by a liver specific promoter...
2016: PloS One
https://www.readbyqxmd.com/read/27866798/long-distance-descending-spinal-neurons-ensure-quadrupedal-locomotor-stability
#17
Ludwig Ruder, Aya Takeoka, Silvia Arber
Locomotion is an essential animal behavior used for translocation. The spinal cord acts as key executing center, but how it coordinates many body parts located across distance remains poorly understood. Here we employed mouse genetic and viral approaches to reveal organizational principles of long-projecting spinal circuits and their role in quadrupedal locomotion. Using neurotransmitter identity, developmental origin, and projection patterns as criteria, we uncover that spinal segments controlling forelimbs and hindlimbs are bidirectionally connected by symmetrically organized direct synaptic pathways that encompass multiple genetically tractable neuronal subpopulations...
November 16, 2016: Neuron
https://www.readbyqxmd.com/read/27863507/transgenic-mice-overexpressing-the-als-linked-protein-matrin-3-develop-a-profound-muscle-phenotype
#18
Christina Moloney, Sruti Rayaprolu, John Howard, Susan Fromholt, Hilda Brown, Matt Collins, Mariela Cabrera, Colin Duffy, Zoe Siemienski, Dave Miller, Maurice S Swanson, Lucia Notterpek, David R Borchelt, Jada Lewis
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of upper and lower motor neurons. Mutations in the gene encoding the nuclear matrix protein Matrin 3 have been found in familial cases of ALS, as well as autosomal dominant distal myopathy with vocal cord and pharyngeal weakness. We previously found that spinal cord and muscle, organs involved in either ALS or distal myopathy, have relatively lower levels of Matrin 3 compared to the brain and other peripheral organs in the murine system...
November 18, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27857722/intra-axonal-protein-synthesis-a-new-target-for-neural-repair
#19
REVIEW
Jeffery L Twiss, Ashley L Kalinski, Rahul Sachdeva, John D Houle
Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthesis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been documented in lamprey, mouse, and rat spinal cord axons...
September 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27856418/spinal-afferent-nerve-endings-in-visceral-organs-recent-advances
#20
Nick J Spencer, Vladimir P Zagorodnyuk, Simon J Brookes, Tim James Hibberd
Spinal afferent neurons play a major role in detection and transduction of painful stimuli from internal (visceral) organs. Recent technical advances have made it possible to visualize the endings of spinal afferent axons in visceral organs. Although it is well known that the sensory nerve cell bodies of spinal afferents reside within dorsal root ganglia (DRG), identifying their endings in internal organs has been especially challenging because of a lack of techniques to distinguish them from endings of other extrinsic and intrinsic neurons (sympathetic, parasympathetic and enteric)...
November 17, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
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