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https://www.readbyqxmd.com/read/28632647/high-osteogenic-potential-of-adipose-and-muscle-derived-mesenchymal-stem-cells-in-spinal-ossification-model-mice
#1
Xizhe Liu, Gentaro Kumagai, Kanichiro Wada, Toshihiro Tanaka, Toru Asari, Kazuki Oishi, Taku Fujita, Hiroki Mizukami, Ken-Ichi Furukawa, Yasuyuki Ishibashi
STUDY DESIGN: Basic experiments in a mouse model of ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To assess the osteogenic potential of mesenchymal stem cells (MSCs) obtained from muscle and adipose tissue in Tiptoe-walking (ttw) mice, in which cervical OPLL compresses the spinal cord and causes motor and sensory dysfunction. SUMMARY OF BACKGROUND DATA: In humans, MSCs have been implicated in the pathogenesis of cervical OPLL...
June 19, 2017: Spine
https://www.readbyqxmd.com/read/28631843/age-related-spontaneous-lumbar-intervertebral-disc-degeneration-in-a-mouse-model
#2
Takashi Ohnishi, Hideki Sudo, Takeru Tsujimoto, Norimasa Iwasaki
The pathogenesis of intervertebral disc degeneration is unclear, but it is a major cause of several spinal diseases. Animal models have historically provided an appropriate benchmark for understanding the human spine. However, there is little information about when intervertebral disc degeneration begins in the mouse or regarding the relationship between magnetic resonance imaging and histological findings. The aim for this study was to obtain information about age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine using magnetic resonance imaging and a histological score regarding when the intervertebral disc degeneration started and how rapidly it progressed, as well as how our histological score detected the degeneration...
June 20, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28629511/microbiota-regulates-visceral-pain-in-the-mouse
#3
Pauline Luczynski, Monica Tramullas, Maria Viola, Fergus Shanahan, Gerard Clarke, Siobhain O'Mahony, Timothy G Dinan, John F Cryan
The perception of visceral pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC)...
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28628111/interaction-of-reactive-astrocytes-with-type-i-collagen-induces-astrocytic-scar-formation-through-the-integrin-n-cadherin-pathway-after-spinal-cord-injury
#4
Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota, Takeyuki Saito, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada
Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28624227/efficient-smn-rescue-following-subcutaneous-tricyclo-dna-antisense-oligonucleotide-treatment
#5
Valérie Robin, Graziella Griffith, John-Paul L Carter, Christian J Leumann, Luis Garcia, Aurélie Goyenvalle
Spinal muscular atrophy (SMA) is a recessive disease caused by mutations in the SMN1 gene, which encodes the protein survival motor neuron (SMN), whose absence dramatically affects the survival of motor neurons. In humans, the severity of the disease is lessened by the presence of a gene copy, SMN2. SMN2 differs from SMN1 by a C-to-T transition in exon 7, which modifies pre-mRNA splicing and prevents successful SMN synthesis. Splice-switching approaches using antisense oligonucleotides (AONs) have already been shown to correct this SMN2 gene transition, providing a therapeutic avenue for SMA...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28624196/evaluation-of-antisense-oligonucleotides-targeting-atxn3-in-sca3-mouse-models
#6
Lauren R Moore, Gautam Rajpal, Ian T Dillingham, Maya Qutob, Kate G Blumenstein, Danielle Gattis, Gene Hung, Holly B Kordasiewicz, Henry L Paulson, Hayley S McLoughlin
The most common dominantly inherited ataxia, spinocerebellar ataxia type 3 (SCA3), is an incurable neurodegenerative disorder caused by a CAG repeat expansion in the ATXN3 gene that encodes an abnormally long polyglutamine tract in the disease protein, ATXN3. Mice lacking ATXN3 are phenotypically normal; hence, disease gene suppression offers a compelling approach to slow the neurodegenerative cascade in SCA3. Here we tested antisense oligonucleotides (ASOs) that target human ATXN3 in two complementary mouse models of SCA3: yeast artificial chromosome (YAC) MJD-Q84...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28622692/motor-deficits-are-independent-of-axonopathy-in-an-alzheimer-s-disease-mouse-model-of-tgcrnd8-mice
#7
Qiuju Yuan, Jian Yang, Wutian Wu, Zhi-Xiu Lin
There have been an increasing number of reports of non-cognitive symptoms in Alzheimer's disease (AD). Some symptoms are associated with the loss of motor functions, e.g. gait disturbances, disturbed activity level and balance. Consistent with clinical findings, several AD mouse models harboring amyloid pathology develop motor impairment. Although the factors that contribute to the motor deficits have not yet been determined, it has been suggested that axonopathy is one of the key factors that may contribute to this particular feature of the disease...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622417/the-antimigraine-butterbur-ingredient-isopetasin-desensitises-peptidergic-nociceptors-via-the-transient-receptor-potential-ankyrin-1-channel
#8
Silvia Benemei, Francesco De Logu, Simone Li Puma, Ilaria Maddalena Marone, Elisabetta Coppi, Filippo Ugolini, Wolfgang Liedtke, Pollastro Federica, Giovanni Appendino, Pierangelo Geppetti, Serena Materazzi, Romina Nassini
BACKGROUND AND PURPOSE: The mechanism of the antimigraine action of butterbur [Petasites hybridus (L.) Gaertn.] is unknown. Here, we investigated the ability of isopetasin, a major butterbur constituent, to specifically target the transient receptor ankyrin 1 (TRPA1) channel and to affect functional responses relevant to migraine. EXPERIMENTAL APPROACH: Single cell calcium imaging and patch-clamp recordings in human and rodent TRPA1-expressing cells, neurogenic motor responses in isolated rat/mouse urinary bladder, release of calcitonin gene-related peptide (CGRP) from mouse spinal cord in vitro, and facial rubbing in mice and meningeal blood flow in rat were examined...
June 16, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28621170/therapeutic-efficacy-of-multipotent-adult-progenitor-cells-versus-mesenchymal-stem-cells-in-experimental-autoimmune-encephalomyelitis
#9
Saurabh Pratap Singh, Sachin Hanumantrao Jadhav, Chandra Prakash Chaturvedi, Soniya Nityanand
AIM: In this study, we have evaluated the therapeutic efficacy of mouse multipotent adult progenitor cells (mMAPCs) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, and compared it with mouse mesenchymal stem cells (mMSCs). MATERIALS & METHODS: We administered PKH26-labeled mMAPC and mMSC into EAE mice and evaluated their therapeutic efficacy. RESULTS: The mMAPC-treated mice in comparison with the mMSC group exhibited a higher suppression of EAE (p < 0...
June 16, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28620692/the-enteric-nervous-system-is-a-potential-autoimmune-target-in-multiple-sclerosis
#10
Marie Wunsch, Samir Jabari, Barbara Voussen, Michael Enders, Shanthi Srinivasan, François Cossais, Thilo Wedel, Martina Boettner, Anna Schwarz, Linda Weyer, Oktay Göcer, Michael Schroeter, Mathias Maeurer, Matthias Woenckhaus, Karolin Pollok, Helena Radbruch, Luisa Klotz, Claus-Jürgen Scholz, Joachim Nickel, Andreas Friebe, Klaus Addicks, Süleyman Ergün, Paul V Lehmann, Stefanie Kuerten
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) in young adults that has serious negative socioeconomic effects. In addition to symptoms caused by CNS pathology, the majority of MS patients frequently exhibit gastrointestinal dysfunction, which was previously either explained by the presence of spinal cord lesions or not directly linked to the autoimmune etiology of the disease. Here, we studied the enteric nervous system (ENS) in a B cell- and antibody-dependent mouse model of MS by immunohistochemistry and electron microscopy at different stages of the disease...
June 15, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28619431/depletion-of-cd20-b-cells-fails-to-inhibit-relapsing-mouse-experimental-autoimmune-encephalomyelitis
#11
Eseberuo Sefia, Gareth Pryce, Ute-Christiane Meier, Gavin Giovannoni, David Baker
BACKGROUND: Multiple sclerosis (MS) is often considered to be a CD4, T cell-mediated disease. This is largely based on the capacity of CD4 T cells to induce relapsing experimental autoimmune encephalomyelitis (EAE) in rodents. However, CD4-depletion using a monoclonal antibody was considered unsuccessful and relapsing MS responds well to B cell depletion via CD20 B cell depleting antibodies. The influence of CD20 B cell depletion in relapsing EAE was assessed. METHODS: Relapsing EAE was induced in Biozzi ABH mice...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28619276/arginine-vasopressin-relates-with-spatial-learning-and-memory-in-a-mouse-model-of-spinocerebellar-ataxia-type-3
#12
Hong-Bo Jiang, Ai-Lin Du, Hai-Yang Luo, Jun Yang, Xiao-Qiu Luo, Rui-Qing Ma, Chang-He Shi, Yu-Ming Xu
Spinocerebellar ataxia is an inherited neurodegenerative disorder that the most prevalent type is type 3 (SCA3). Arginine vasopressin (AVP) is released within the lateral septum for controlling the learning and memory. This communication studied the effect of AVP on the spatial learning and memory of SCA3 mice. The spatial learning and memory were analyzed by Morris water maze test (MWM), and AVP concentration was measured by radioimmunoassay. The results showed that (Alves et al., 2010) the swimming velocity, distance traveled and latency to the platform of MWM in SCA3 mice were reduced slower than those in WT mice over 4 training days (p<0...
June 6, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28618739/an-investigation-of-sagittal-thoracic-spinal-curvature-and-mobility-in-subjects-with-and-without-chronic-neck-pain-cut-off-points-and-pain-relationship
#13
Derya Özer Kaya, Şeyda Toprak Çelenay
BACKGROUND/AIM: Thoracic spine insufficiency is a subject of interest in neck problems. The aim was to investigate thoracic spinal curvature and mobility in subjects with and without chronic neck pain (CNP), cut-off points, and the relationship with pain. MATERIALS AND METHODS: Fifty-six patients with CNP (CNP group) and 53 healthy volunteers (control group) were included. Neck pain intensity of the patients was assessed by visual analogue scale and sagittal thoracic curvature and mobility of all participants were assessed by Spinal Mouse (Idiag, Fehraltorf, Switzerland)...
June 12, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28607062/biomechanical-coupling-facilitates-spinal-neural-tube-closure-in-mouse-embryos
#14
Gabriel L Galea, Young-June Cho, Gauden Galea, Matteo A Molè, Ana Rolo, Dawn Savery, Dale Moulding, Lucy H Culshaw, Evanthia Nikolopoulou, Nicholas D E Greene, Andrew J Copp
Neural tube (NT) formation in the spinal region of the mammalian embryo involves a wave of "zippering" that passes down the elongating spinal axis, uniting the neural fold tips in the dorsal midline. Failure of this closure process leads to open spina bifida, a common cause of severe neurologic disability in humans. Here, we combined a tissue-level strain-mapping workflow with laser ablation of live-imaged mouse embryos to investigate the biomechanics of mammalian spinal closure. Ablation of the zippering point at the embryonic dorsal midline causes far-reaching, rapid separation of the elevating neural folds...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28606623/the-interaction-between-alpha-7-nicotinic-acetylcholine-receptor-and-nuclear-peroxisome-proliferator-activated-receptor-%C3%AE-represents-a-new-antinociceptive-signaling-pathway-in-mice
#15
Giulia Donvito, Deniz Bagdas, Wisam Toma, Elnaz Rahimpour, Asti Jackson, Julie A Meade, Shakir AlSharari, Abhijit R Kulkarni, F Ivy Carroll, Aron H Lichtman, Roger L Papke, Ganesh A Thakur, M Imad Damaj
Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modulated by positive allosteric modulators (PAMs), ago-allosteric ligands (ago-PAMs), and α7-silent agonists. Activation of α7 nAChRs has been reported to increase the brain levels of endogenous ligands for nuclear peroxisome proliferator-activated receptors type-α (PPAR-α), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in a Ca(2+)-dependent manner...
June 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28603559/three-immune-mediated-disease-models-induced-by-theiler-s-virus-multiple-sclerosis-seizures-and-myocarditis
#16
Ikuo Tsunoda, Fumitaka Sato, Seiichi Omura, Mitsugu Fujita, Namie Sakiyama, Ah-Mee Park
Theiler's murine encephalomyelitis virus (TMEV) infection has been used as a viral model for multiple sclerosis (MS), as TMEV can induce chronic inflammatory demyelinating lesions with viral persistence in the spinal cord of SJL/J mice. In contrast, when C57BL/6 mice are infected with TMEV, the mice can clear the virus from the central nervous system (CNS), without viral persistence or demyelination, but develop seizures and hippocampal sclerosis, which has been used as a viral model for seizures/epilepsy. In the two TMEV-induced CNS disease models, not only viral infection, but also immune responses contribute to the pathogenesis...
November 2016: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/28603486/comparison-of-sirtuin-3-levels-in-als-and-huntington-s-disease-differential-effects-in-human-tissue-samples-vs-transgenic-mouse-models
#17
Eva Buck, Hanna Bayer, Katrin S Lindenberg, Johannes Hanselmann, Noemi Pasquarelli, Albert C Ludolph, Patrick Weydt, Anke Witting
Neurodegenerative diseases are characterized by distinct patterns of neuronal loss. In amyotrophic lateral sclerosis (ALS) upper and lower motoneurons degenerate whereas in Huntington's disease (HD) medium spiny neurons in the striatum are preferentially affected. Despite these differences the pathophysiological mechanisms and risk factors are remarkably similar. In addition, non-neuronal features, such as weight loss implicate a dysregulation in energy metabolism. Mammalian sirtuins, especially the mitochondrial NAD+ dependent sirtuin 3 (SIRT3), regulate mitochondrial function and aging processes...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28600752/rapamycin-ameliorates-experimental-autoimmune-encephalomyelitis-by-suppressing-the-mtor-stat3-pathway
#18
Huiqing Hou, Jun Miao, Runjing Cao, Mei Han, Yafei Sun, Xiaoqian Liu, Li Guo
Rapamycin is a new immunosuppressant that has a primarily anti-inflammatory effect and selectively inhibits the activation of T helper (Th)-cell subsets. It is widely used to treat autoimmune disease. We studied the mechanism of rapamycin action against experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a classic animal model of multiple sclerosis. Rapamycin significantly inhibited the development of EAE by decreasing both clinical scores and inflammatory cell infiltration into the spinal cord...
May 30, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28599923/silencing-of-the-rna-binding-protein-hur-attenuates-hyperalgesia-and-motor-disability-in-experimental-autoimmune-encephalomyelitis
#19
Maria Domenica Sanna, Alessandro Quattrone, Nicoletta Galeotti
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system associated with progressive neuronal loss and axonal degeneration. Neuronal lesions and dysfunction lead often to neuropathic pain, the most prevalent and difficult to treat pain syndrome observed in MS patients. Despite its widespread occurrence, the underlying neural mechanisms for MS pain are not fully understood. For a better clarification of the pathophysiology of MS-associated pain, we investigated the role of HuR, an RNA-binding protein that positively regulates the stability of many target mRNAs, including several cytokines...
June 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28598854/analysis-of-azithromycin-monohydrate-as-a-single-or-a-combinatorial-therapy-in-a-mouse-model-of-severe-spinal-muscular-atrophy
#20
Erkan Y Osman, Charles W Washington, Madeline E Simon, Dalia Megiddo, Dalia Hagar Greif, Christian L Lorson
BACKGROUND: Spinal muscular atrophy (SMA) is a neurodegenerative autosomal recessive disorder characterized by the loss of α-motor neurons. A variety of molecular pathways are being investigated to elevate SMN protein expression in SMA models and in the clinic. One of these approaches involves stabilizing the SMNΔ7 protein by inducing translational read-through. Previous studies have demonstrated that functionality and stability are partially restored to the otherwise unstable SMNΔ7 by the addition of non-specific C-terminal peptide sequences, or by inducing a similar molecular event through the use of read-through inducing compounds such as aminoglycosides...
June 9, 2017: Journal of Neuromuscular Diseases
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