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https://www.readbyqxmd.com/read/28821921/anti-nociceptive-effect-of-stigmasterol-in-mouse-models-of-acute-and-chronic-pain
#1
Cristiani Isabel Banderó Walker, Sara Marchesan Oliveira, Raquel Tonello, Mateus Fortes Rossato, Evelyne da Silva Brum, Juliano Ferreira, Gabriela Trevisan
Stigmasterol is a common sterol found in plants, but the anti-nociceptive effect of this compound and its mechanism of action are not fully explored. Thus, in the present study, the anti-nociceptive effect of stigmasterol was investigated in acute and chronic models of pain and its mechanism of action. We used adult male albino Swiss mice (25-35 g) to observe the anti-nociceptive effect of stigmasterol in acetic-acid writhing test or in complete Freund's adjuvant injection, surgical incision in hind paw, or partial sciatic nerve ligation...
August 18, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28821644/calpain-dependent-degradation-of-nucleoporins-contributes-to-motor-neuron-death-in-a-mouse-model-of-chronic-excitotoxicity
#2
Kaori Sugiyama, Tomomi Aida, Masatoshi Nomura, Ryoichi Takayanagi, Hanns U Zeilhofer, Kohichi Tanaka
Glutamate-mediated excitotoxicity induces neuronal death by altering various intracellular signaling pathways and is implicated as a common pathogenic pathway in many neurodegenerative diseases. In the case of motor neuron disease, there is significant evidence to suggest that overactivation of AMPA receptors due to deficiencies in the expression and function of glial glutamate transporter GLT1 and GLAST plays an important role in the mechanisms of neuronal death. However, a causal role for glial glutamate transporter dysfunction in motor neuron death remains unknown...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821396/the-new-hdac1-inhibitor-lg325-ameliorates-neuropathic-pain-in-a-mouse-model
#3
Maria Domenica Sanna, Luca Guandalini, Maria Novella Romanelli, Nicoletta Galeotti
Current analgesic therapies for treatment of neuropathic pain are unsatisfactory. Neuropathic pain is, therefore, undertreated and there is a significant need for a better pharmacotherapy. Increasing evidence indicate that histone deacetylation is a critical step in nerve injury pain. To obtain an innovative treatment for the management of neuropathic pain, we investigated the pharmacological effects produced by the new histone deacetylase (HDAC)-1 selective inhibitor, LG325, in a mouse model of trauma-induced peripheral mononeuropathy provoked by spared nerve injury (SNI)...
August 15, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28816271/-construction-and-improvement-of-animal-models-with-different-positional-osseous-metastasis-of-prostate-cancer-in-vivo
#4
Y X Bi, M H Xiao, N N Zhang, X Y Li, X P Mao, K Zhang, Z R Zhang, L Y Zhao
OBJECTIVE: To provide an important tool for the study of diagnose and treatment of prostate cancer (PCa) osseous metastasis and change of bone stress force on prostate cancer (PCa) osseous metastasis and a platform, which is more congruous to clinical process, for prevention and cure of neoplastic bone metastases, and to carry out the construction and improvement of animal models of PCa with different positional osseous metastasis in vivo. METHODS: Different gradient concentrations of RM-1 cells were inoculated into the cavity of left femoral bone or lumbar vertebra of mice (C57BL/6) respectively...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28816231/molecular-mechanisms-of-the-analgesic-action-of-wu-tou-decoction-on-neuropathic-pain-in-mice-revealed-using-microarray-and-network-analysis
#5
Yan-Qiong Zhang, Chao Wang, Qiu-Yan Guo, Chun-Yan Zhu, Chen Yan, Dan-Ni Sun, Qiong-Hong Xu, Na Lin
Wu-tou Decoction (WTD) is a classic herbal formula in traditional Chinese medicine for the treatment of joint diseases, neuropathic pain (NP) and inflammatory pain. In this study we investigated whether WTD produced analgesic action in a mouse spinal nerve ligation (SNL) model and elucidated the underlying molecular mechanisms. Mice were subjected to SNL and orally treated with WTD (3.15, 6.30 or 12.60 g·kg(-1)·d(-1)) for 21 d. SNL induced mechanical hyperalgesia and heat hyperalgesia characterized by rapid and persistent pain hypersensitivity...
August 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28808928/regulation-of-survival-motor-neuron-protein-by-the-nuclear-factor-kappa-b-pathway-in-mouse-spinal-cord-motoneurons
#6
Saravanan Arumugam, Stefka Mincheva-Tasheva, Ambika Periyakaruppiah, Sandra de la Fuente, Rosa M Soler, Ana Garcera
Survival motor neuron (SMN) protein deficiency causes the genetic neuromuscular disorder spinal muscular atrophy (SMA), characterized by spinal cord motoneuron degeneration. Since SMN protein level is critical to disease onset and severity, analysis of the mechanisms involved in SMN stability is one of the central goals of SMA research. Here, we describe the role of several members of the NF-κB pathway in regulating SMN in motoneurons. NF-κB is one of the main regulators of motoneuron survival and pharmacological inhibition of NF-κB pathway activity also induces mouse survival motor neuron (Smn) protein decrease...
August 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28807781/engrailed-controls-epaxial-hypaxial-muscle-innervation-and-the-establishment-of-vertebrate-three-dimensional-mobility
#7
Mohi U Ahmed, Ashish K Maurya, Louise Cheng, Erika C Jorge, Frank R Schubert, Pascal Maire, M Albert Basson, Philip W Ingham, Susanne Dietrich
Chordates are characterised by contractile muscle on either side of the body that promotes movement by side-to-side undulation. In the lineage leading to modern jawed vertebrates (crown group gnathostomes), this system was refined: body muscle became segregated into distinct dorsal (epaxial) and ventral (hypaxial) components that are separately innervated by the medial and hypaxial motors column, respectively, via the dorsal and ventral ramus of the spinal nerves. This allows full three-dimensional mobility, which in turn was a key factor in their evolutionary success...
August 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28807492/neuropsychiatric-involvement-in-lupus-is-associated-with-the-nogo-a-ngr1-pathway
#8
Hong-Wei Lei, Jing-Yuan Wang, Qiu-Jie Dang, Fan Yang, Xin Liu, Ji-Hui Zhang, Yang Li
Neuroinflammation- and neurodegeneration-induced nerve injury may represent important components of neuropsychiatric lupus (NPSLE). Myelin-associated neurite outgrowth inhibitor (Nogo)-a and its receptor, NgR1, limit recovery of the adult central nervous system after injury. We detected a soluble Nogo-a product in the cerebral spinal fluid of patients with NPSLE. In a mouse model of lupus, aging was associated with an increase in Nogo-a positive neurons, diminished myelin sheaths, enhanced pro-inflammatory cytokines, and impaired cognition and memory...
July 9, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28807414/transient-receptor-potential-vanilloid-4-expressing-macrophages-and-keratinocytes-contribute-differentially-to-allergic-and-nonallergic-chronic-itch
#9
Jialie Luo, Jing Feng, Guang Yu, Pu Yang, Madison R Mack, Junhui Du, Weihua Yu, Aihua Qian, Yujin Zhang, Shenbin Liu, Shijin Yin, Amy Xu, Jizhong Cheng, Qingyun Liu, Roger G O'Neil, Yang Xia, Liang Ma, Susan M Carlton, Brian S Kim, Kenneth Renner, Qin Liu, Hongzhen Hu
BACKGROUND: Chronic itch is a highly debilitating symptom that underlies many medical disorders with no universally effective treatments. Although unique neuronal signaling cascades in the sensory ganglia and spinal cord have been shown to critically promote the pathogenesis of chronic itch, the role of skin-associated cells remains poorly understood. OBJECTIVE: We sought to examine the cutaneous mechanisms underlying transient receptor potential vanilloid 4 (TRPV4)-mediated allergic and nonallergic chronic itch...
August 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28791352/establishment-of-a-murine-pancreatic-cancer-pain-model-and-microarray-analysis-of-pain%C3%A2-associated-genes-in-the-spinal-cord-dorsal-horn
#10
Liqin Wang, Huihong Xu, Yanhu Ge, Hai Zhu, Dawei Yu, Weifeng Yu, Zhijie Lu
There is emerging evidence on the mechanisms of pancreatic cancer pain. Following the establishment of an orthotropic transplantation model of pancreatic cancer, microarray analysis was performed to identify changes in the expression levels of pain‑associated genes in the spinal cord. A mouse model of pancreatic cancer‑induced pain was established by implanting SW 1990 cells into the pancreases of female BALB/c‑nu mice. The survival rate and body weight were measured following orthotropic transplantation...
August 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28776347/the-anti-inflammatory-effects-of-oral-formulated-tacrolimus-in-mice-with-experimental-autoimmune-encephalomyelitis
#11
Myung Jin Kim, Jung Joon Sung, Seung Hyun Kim, Jeong Min Kim, Gye Sun Jeon, Seog Kyun Mun, Suk Won Ahn
Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group...
September 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28775379/tia1-is-a-gender-specific-disease-modifier-of-a-mild-mouse-model-of-spinal-muscular-atrophy
#12
Matthew D Howell, Eric W Ottesen, Natalia N Singh, Rachel L Anderson, Joonbae Seo, Senthilkumar Sivanesan, Elizabeth M Whitley, Ravindra N Singh
Spinal muscular atrophy (SMA) is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. The nearly identical SMN2 cannot compensate for SMN1 loss due to exon 7 skipping. The allele C (C (+/+)) mouse recapitulates a mild SMA-like phenotype and offers an ideal system to monitor the role of disease-modifying factors over a long time. T-cell-restricted intracellular antigen 1 (TIA1) regulates SMN exon 7 splicing. TIA1 is reported to be downregulated in obese patients, although it is not known if the effect is gender-specific...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28771723/-prion-like-propagation-of-the-synucleinopathy-of-m83-transgenic-mice-depends-on-the-mouse-genotype-and-type-of-inoculum
#13
Dorian Sargent, Jérémy Verchere, Corinne Lazizzera, Damien Gaillard, Latifa Lakhdar, Nathalie Streichenberger, Eric Morignat, Dominique Bétemps, Thierry Baron
The M83 transgenic mouse is a model of human synucleinopathies that develops severe motor impairment correlated with accumulation of the pathological Ser129-phosphorylated α-synuclein (α-syn(P) ) in the brain and spinal cord. M83 disease can be accelerated by intracerebral inoculation of brain extracts from sick M83 mice. This has also recently been described using peripheral routes, injecting recombinant preformed α-syn fibrils into the muscle or the peritoneum. Here, we inoculated homozygous and/or hemizygous M83 neonates via the intraperitoneal and/or intracerebral routes with two different brain extracts: one from sick M83 mice inoculated with brain extract from other sick M83 mice, and the other derived from a human multiple system atrophy (MSA) source passaged in M83 mice...
August 3, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28769766/breakthrough-cancer-pain-is-associated-with-spinal-gap-junction-activation-via-regulation-of-connexin-43-in-a-mouse-model
#14
Xin Li, Siqing Jiang, Hui Yang, Qian Liao, Shousong Cao, Xuebin Yan, Dong Huang
Breakthrough cancer pain (BTcP) is a high-intensity, short-duration, unpredictable and uncontrollable pain. Recent studies have shown that activation of gap junction (GJ) in spinal cord plays an important role in the pathogenesis of BTcP. We examined the expressions of Glial fibrillary acidic protein (GFAP), connexin (Cx) 43 protein and phosphorylation of Cx43 (p-Cx43) in the spinal cord of mice. In addition, we investigated the effects of Gap26, a selective GJ blocker, on the expressions of GFAP, Cx43 and p-Cx43 in BTcP mice...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28768912/single-cell-profiling-reveals-gpcr-heterogeneity-and-functional-patterning-during-neuroinflammation
#15
Denise Tischner, Myriam Grimm, Harmandeep Kaur, Daniel Staudenraus, Jorge Carvalho, Mario Looso, Stefan Günther, Florian Wanke, Sonja Moos, Nelly Siller, Johanna Breuer, Nicholas Schwab, Frauke Zipp, Ari Waisman, Florian C Kurschus, Stefan Offermanns, Nina Wettschureck
GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to expression in individual cells. Here, we show a microfluidic-based single-cell GPCR expression analysis in primary T cells, myeloid cells, and endothelial cells under naive conditions and during experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis. We found that neuroinflammation induces characteristic changes in GPCR heterogeneity and patterning, and we identify various functionally relevant subgroups with specific GPCR profiles among spinal cord-infiltrating CD4 T cells, macrophages, microglia, or endothelial cells...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28764573/human-periodontal-ligament-stem-cells-secretome-from-multiple-sclerosis-patients-suppresses-nalp3-inflammasome-activation-in-experimental-autoimmune-encephalomyelitis
#16
Thangavelu Soundara Rajan, Sabrina Giacoppo, Francesca Diomede, Placido Bramanti, Oriana Trubiani, Emanuela Mazzon
Research in recent years has largely explored the immunomodulatory effects of mesenchymal stem cells (MSCs) and their secretory products, called "secretome," in the treatment of neuroinflammatory diseases. Here, we examined whether such immunosuppressive effects might be elicited due to inflammasome inactivation. To this end, we treated experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis (MS) with the conditioned medium or purified exosomes/microvesicles (EMVs) obtained from relapsing-remitting-MS patients human periodontal ligament stem cells (hPDLSCs) and investigated the regulation of NALP3 inflammasome...
August 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28763002/toll-like-receptor-4-inhibitor-tak-242-attenuates-motor-dysfunction-and-spinal-cord-pathology-in-an-amyotrophic-lateral-sclerosis-mouse-model
#17
Avi Fellner, Yael Barhum, Ariel Angel, Nisim Perets, Israel Steiner, Daniel Offen, Nirit Lev
Neuroinflammation contributes to amyotrophic lateral sclerosis (ALS) progression. TLR4, a transmembrane protein that plays a central role in activation of the innate immune system, has been shown to induce microglial activation in ALS models. TLR4 is up-regulated in the spinal cords of hSOD1(G93A) mice. We aimed to examine the effects of specific TLR4 inhibition on disease progression and survival in the hSOD1(G93A) mouse model of ALS. Immunologic effect of TLR4 inhibition in vitro was measured by the effect of TAK-242 treatment on LPS-induced splenocytes proliferation...
August 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28762472/absence-of-notch1-in-murine-myeloid-cells-attenuates-the-development-of-experimental-autoimmune-encephalomyelitis-by-affecting-th1-and-th17-priming
#18
Miriam Fernández, Eva M Monsalve, Susana López-López, Almudena Ruiz-García, Susana Mellado, Elena Caminos, José Javier García-Ramírez, Jorge Laborda, Pedro Tranque, María José M Díaz-Guerra
Inhibition of Notch signalling in T cells attenuates the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Growing evidence indicates that myeloid cells are also key players in autoimmune processes. Thus, the present study evaluates the role of the Notch1 receptor in myeloid cells on the progression of myelin oligodendrocyte glycoprotein (MOG)35-55 -induced EAE, using mice with a myeloid-specific deletion of the Notch1 gene (MyeNotch1KO). We found that EAE progression was less severe in the absence of Notch1 in myeloid cells...
August 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28755985/peripheral-and-central-sites-of-action-for-anti-allodynic-activity-induced-by-the-bifunctional-opioid-npff-receptors-agonist-bn-9-in-inflammatory-pain-model
#19
Run Zhang, Biao Xu, Meng-Na Zhang, Ting Zhang, Zi-Long Wang, Geng Zhao, Guang-Hai Zhao, Ning Li, Quan Fang, Rui Wang
The activation of opioid and neuropeptide FF (NPFF) receptors plays important roles to modulate nociceptive signal in inflammatory pain states. Recently, BN-9 (Tyr-D.Ala-Gly-Phe-Gln-Pro-Gln-Arg-Phe-NH2) was pharmacologically characterized as a novel bifunctional agonist at both opioid and NPFF receptors. In the present study, the anti-allodynic activity and site(s) of action of BN-9 were assessed in a mouse model of carrageenan-induced inflammatory pain. In mice, BN-9 induced a dose-dependent anti-allodinic effect through opioid receptor at supraspinal or spinal level, and this effect was augmented by pretreatment with the NPFF receptor antagonist at the same level...
July 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28751457/2-arachidonoylglycerol-reduces-proteoglycans-and-enhances-remyelination-in-a-progressive-model-of-demyelination
#20
A Feliu, Bonilla I Del Río, F J Carrillo-Salinas, G Hernández-Torres, L Mestre, N Puente, S Ortega-Gutiérrez, M L López-Rodríguez, P Grandes, M Mecha, C Guaza
The failure to undergo remyelination is a critical impediment to recovery in multiple sclerosis (MS). Chondroitin sulfate proteoglycans (CSPGs) accumulate at demyelinating lesions creating a non-permissive environment that impairs axon regeneration and remyelination. Here, we reveal a new role for 2-arachinonoylglycerol (2-AG), the major CNS endocannabinoid, in the modulation of CSPG deposition in a progressive model of MS, the Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD)...
July 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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