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https://www.readbyqxmd.com/read/29053899/peptidergic-nerve-fibers-in-the-urethra-morphological-and-neurochemical-characteristics-in-female-mice-of-reproductive-age
#1
Christine M Barry, Esther Ji, Harman Sharma, Pauline Yap, Nicholas J Spencer, Dusan Matusica, Rainer V Haberberger
BACKGROUND: Peptidergic nerve fibers provide important contributions to urethral function. Urethral innervation of female mice is not well documented. AIMS: To determine the distribution and projection sites of nerve fibers immunoreactive for vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) in the urethra of wild-type control mice and compare innervation characteristics between the proximal and distal urethra of young nullipara and older multipara mice...
October 20, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29051763/il-12p35-inhibits-neuroinflammation-and-ameliorates-autoimmune-encephalomyelitis
#2
Jin Kyeong Choi, Ivy M Dambuza, Chang He, Cheng-Rong Yu, Anita N Uche, Mary J Mattapallil, Rachel R Caspi, Charles E Egwuagu
Multiple sclerosis (MS) is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE), the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29049317/identification-of-genome-wide-targets-of-olig2-in-the-adult-mouse-spinal-cord-using-chip-seq
#3
Andrew J Darr, Matt C Danzi, Lee Brady, Dorothea Emig-Agius, Amber Hackett, Roozbeh Golshani, Nikita Warner, Jae Lee, Vance P Lemmon, Pantelis Tsoulfas
In jawed vertebrates, oligodendrocytes (OLs) are the myelin-producing glial cells responsible for ensheathment of axons within the central nervous system and are also crucial for remyelination following injury or disease. Olig2 is a crucial factor in the specification and differentiation of oligodendrocyte precursor cells (OPCs) that give rise to mature, myelin-producing OLs in the developing and postnatal CNS; however, its role in adulthood is less well understood. To investigate the role Olig2 plays in regulating gene expression in the adult OL lineage in a physiologically-relevant context, we performed chromatin immunoprecipitation followed by next generation sequencing analysis (ChIP-Seq) using whole spinal cord tissue harvested from adult mice...
2017: PloS One
https://www.readbyqxmd.com/read/29039596/the-role-of-the-mir-99b-5p-mtor-signaling-pathway-in-neuroregeneration-in-mice-following-spinal-cord-injury
#4
Fujiang Cao, Tao Liu, Shiwei Sun, Shiqing Feng
The present study aimed to investigate the role of microRNA (miR)‑99b‑5p in spinal cord injury (SCI). Reverse transcription‑quantitative polymerase chain reaction demonstrated that, compared with control mice, the expression levels of miR‑99b‑5p were upregulated in the mouse spinal cord following SCI. Mechanistic target of rapamycin (mTOR) was predicted to be the possible target of miR‑99b‑5p according to TargetScan and microrna databases. Dual‑luciferase reporter assay verified that miR‑99b‑5p was able to target mTOR...
October 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29038439/analysis-of-nkx3-1-cre-driven-erk5-deletion-reveals-a-profound-spinal-deformity-which-is-linked-to-increased-osteoclast-activity
#5
Carolyn J Loveridge, Rob J van 't Hof, Gemma Charlesworth, Ayala King, Ee Hong Tan, Lorraine Rose, Anna Daroszewska, Amanda Prior, Imran Ahmad, Michelle Welsh, Ernest J Mui, Catriona Ford, Mark Salji, Owen Sansom, Karen Blyth, Hing Y Leung
Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5 (fl/fl) (Erk5 (fl/fl)) mice by ~6-8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5 (fl/fl) mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29033792/spontaneous-and-evoked-activity-from-murine-ventral-horn-cultures-on-microelectrode-arrays
#6
Bryan J Black, Rahul Atmaramani, Joseph J Pancrazio
Motor neurons are the site of action for several neurological disorders and paralytic toxins, with cell bodies located in the ventral horn (VH) of the spinal cord along with interneurons and support cells. Microelectrode arrays (MEAs) have emerged as a high content assay platform for mechanistic studies and drug discovery. Here, we explored the spontaneous and evoked electrical activity of VH cultures derived from embryonic mouse spinal cord on multi-well plates of MEAs. Primary VH cultures from embryonic day 15-16 mice were characterized by expression of choline acetyltransferase (ChAT) by immunocytochemistry...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29029628/erythropoietin-reduces-experimental-autoimmune-encephalomyelitis-severity-via-neuroprotective-mechanisms
#7
M Moransard, M Bednar, K Frei, M Gassmann, O O Ogunshola
BACKGROUND: Treatment with erythropoietin (Epo) in experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis (MS), has consistently been shown to ameliorate disease progression and improve overall outcome. The effect has been attributed to modulation of the immune response and/or preservation of the central nervous system (CNS) tissue integrity. It remains unclear, however, if (a) Epo acts primarily in the CNS or the periphery and if (b) Epo's beneficial effect in EAE is mainly due to maintaining CNS tissue integrity or to modulation of the immune response...
October 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29027761/oxidative-stress-and-mitochondrial-dynamics-malfunction-are-linked-in-pelizaeus-merzbacher-disease
#8
Montserrat Ruiz, Mélina Bégou, Nathalie Launay, Pablo Ranea-Robles, Patrizia Bianchi, Jone López-Erauskin, Laia Morató, Cristina Guilera, Bérengère Petit, Catherine Vaurs-Barriere, Céline Guéret-Gonthier, Marie-Noëlle Bonnet-Dupeyron, Stéphane Fourcade, Johan Auwerx, Odile Boespflug-Tanguy, Aurora Pujol
Pelizaeus-Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD...
October 13, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29026895/non-radiographic-methods-of-measuring-global-sagittal-balance-a-systematic-review
#9
REVIEW
Larry Cohen, Sarah Kobayashi, Milena Simic, Sarah Dennis, Kathryn Refshauge, Evangelos Pappas
BACKGROUND: Global sagittal balance, describing the vertical alignment of the spine, is an important factor in the non-operative and operative management of back pain. However, the typical gold standard method of assessment, radiography, requires exposure to radiation and increased cost, making it unsuitable for repeated use. Non-radiologic methods of assessment are available, but their reliability and validity in the current literature have not been systematically assessed. Therefore, the aim of this systematic review was to synthesise and evaluate the reliability and validity of non-radiographic methods of assessing global sagittal balance...
2017: Scoliosis and Spinal Disorders
https://www.readbyqxmd.com/read/29022879/sparse-genetic-tracing-reveals-regionally-specific-functional-organization-of-mammalian-nociceptors
#10
William Olson, Ishmail Abdus-Saboor, Lian Cui, Justin Burdge, Tobias Raabe, Minghong Ma, Wenqin Luo
The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd(CreERT2) mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd(+) nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord...
October 12, 2017: ELife
https://www.readbyqxmd.com/read/29021610/low-immunogenicity-of-mouse-induced-pluripotent-stem-cell-derived-neural-stem-progenitor-cells
#11
Go Itakura, Masahiro Ozaki, Narihito Nagoshi, Soya Kawabata, Yuichiro Nishiyama, Keiko Sugai, Tsuyoshi Iida, Rei Kashiwagi, Toshiki Ookubo, Kaori Yastake, Kohei Matsubayashi, Jun Kohyama, Akio Iwanami, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano
Resolving the immunogenicity of cells derived from induced pluripotent stem cells (iPSCs) remains an important challenge for cell transplant strategies that use banked allogeneic cells. Thus, we evaluated the immunogenicity of mouse fetal neural stem/progenitor cells (fetus-NSPCs) and iPSC-derived neural stem/progenitor cells (iPSC-NSPCs) both in vitro and in vivo. Flow cytometry revealed the low expression of immunological surface antigens, and these cells survived in all mice when transplanted syngeneically into subcutaneous tissue and the spinal cord...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29017855/role-of-neuromedin-u-in-accelerating-of-non-alcoholic-steatohepatitis-in-mice
#12
Hitoshi Teranishi, Masafumi Hayashi, Ryoko Higa, Kenji Mori, Takashi Miyazawa, Jun Hino, Yuichiro Amano, Ryuichi Tozawa, Takanori Ida, Toshikatsu Hanada, Mikiya Miyazato, Reiko Hanada, Kenji Kangawa, Kazuwa Nakao
Neuromedin U (NMU), a neuropeptide originally isolated from porcine spinal cord, has multiple physiological functions and is involved in obesity and inflammation. Excessive fat accumulation in the liver leads to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which is closely associated with obesity. NAFLD and NASH develop and progress via complex pathophysiological processes, and it remains unclear to what extend the NMU system contributes to the risk of obesity-related disorders such as NAFLD and NASH...
October 7, 2017: Peptides
https://www.readbyqxmd.com/read/29016438/ono-1301-enhances-in-vitro-osteoblast-differentiation-and-in-vivo-bone-formation-induced-by-bone-morphogenetic-protein
#13
Sadaaki Kanayama, Takashi Kaito, Kazuma Kitaguchi, Hiroyuki Ishiguro, Kunihiko Hashimoto, Ryota Chijimatsu, Satoru Otsuru, Shota Takenaka, Takahiro Makino, Yusuke Sakai, Akira Myoui, Hideki Yoshikawa
STUDY DESIGN: In vitro and in vivo assessment of osteogenic effect by prostacyclin agonist (ONO-1301) OBJECTIVE.: To investigate the effects of ONO-1301 on in vitro osteoblastic differentiation and in vivo bone formation induced by bone morphogenetic protein (BMP). SUMMARY OF BACKGROUND DATA: Among prostaglandins (PGs), PGE2 is the most abundant in bone tissue and its effects on bone formation have been well studied. PGI2 (prostacyclin) is the second most abundant PG in bone tissue and plays important roles in hemodynamics...
October 9, 2017: Spine
https://www.readbyqxmd.com/read/28991854/alkali-burn-induced-corneal-spontaneous-pain-and-activated-neuropathic-pain-matrix-in-the-central-nervous-system-in-mice
#14
Yan Xiang, Wenchang Zhou, Ping Wang, Hui Yang, Feng Gao, Hongbin Xiang, Anne Manyande, Yuke Tian, Xuebi Tian
PURPOSE: To explore whether alkali burn causes corneal neuropathic pain and activates the neuropathic pain matrix in the central nervous system in mice. METHODS: A corneal alkali burn mouse model (grade II) was used. The mechanical threshold in the cauterized area was tested using Von Frey hairs. Spontaneous pain behavior was investigated with conditioned place preference. Phosphor extracellular signal-regulated kinase (ERK), which is a marker for neuronal activation in chronic pain processing, was investigated in several representative areas of the neuropathic pain matrix: the 2 regions of the spinal trigeminal nucleus (subnucleus interpolaris/caudalis, Vi/Vc; subnucleus caudalis/upper cervical cord, Vc/C1), insular cortex, anterior cingulated cortex (ACC), and the rostroventral medulla (RVM)...
November 2017: Cornea
https://www.readbyqxmd.com/read/28990928/mouse-embryonic-stem-cells-can-differentiate-via-multiple-paths-to-the-same-state
#15
James Alexander Briggs, Victor C Li, Seungkyu Lee, Clifford J Woolf, Allon Klein, Marc W Kirschner
In embryonic development, cells differentiate through stereotypical sequences of intermediate states to generate particular mature fates. By contrast, driving differentiation by ectopically expressing terminal transcription factors (direct programming) can generate similar fates by alternative routes. How differentiation in direct programming relates to embryonic differentiation is unclear. We applied single-cell RNA sequencing to compare two motor neuron differentiation protocols: a standard protocol approximating the embryonic lineage, and a direct programming method...
October 9, 2017: ELife
https://www.readbyqxmd.com/read/28986540/reactive-metabolites-of-acetaminophen-activate-and-sensitize-the-capsaicin-receptor-trpv1
#16
Mirjam J Eberhardt, Florian Schillers, Esther M Eberhardt, Linus Risser, Jeanne de la Roche, Christine Herzog, Frank Echtermeyer, Andreas Leffler
The irritant receptor TRPA1 was suggested to mediate analgesic, antipyretic but also pro-inflammatory effects of the non-opioid analgesic acetaminophen, presumably due to channel activation by the reactive metabolites parabenzoquinone (pBQ) and N-acetyl-parabenzoquinonimine (NAPQI). Here we explored the effects of these metabolites on the capsaicin receptor TRPV1, another redox-sensitive ion channel expressed in sensory neurons. Both pBQ and NAPQI, but not acetaminophen irreversibly activated and sensitized recombinant human and rodent TRPV1 channels expressed in HEK 293 cells...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28986144/motor-axons-are-guided-to-exit-points-in-the-spinal-cord-by-slit-and-netrin-signals
#17
Minkyung Kim, Tatiana M Fontelonga, Clare H Lee, Sarah J Barnum, Grant S Mastick
In the spinal cord, motor axons project out the neural tube at specific exit points, then bundle together to project toward target muscles. The molecular signals that guide motor axons to and out of their exit points remain undefined. Since motor axons and their exit points are located near the floor plate, guidance signals produced by the floor plate and adjacent ventral tissues could influence motor axons as they project toward and out of exit points. The secreted Slit proteins are major floor plate repellents, and motor neurons express two Slit receptors, Robo1 and Robo2...
October 3, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28980850/rilmenidine-promotes-mtor-independent-autophagy-in-the-mutant-sod1-mouse-model-of-amyotrophic-lateral-sclerosis-without-slowing-disease-progression
#18
Nirma D Perera, Rebecca K Sheean, Chew L Lau, Yea Seul Shin, Philip M Beart, Malcolm K Horne, Bradley J Turner
Macroautophagy/autophagy is the main intracellular catabolic pathway in neurons that eliminates misfolded proteins, aggregates and damaged organelles associated with ageing and neurodegeneration. Autophagy is regulated by both MTOR-dependent and -independent pathways. There is increasing evidence that autophagy is compromised in neurodegenerative disorders, which may contribute to cytoplasmic sequestration of aggregation-prone and toxic proteins in neurons. Genetic or pharmacological modulation of autophagy to promote clearance of misfolded proteins may be a promising therapeutic avenue for these disorders...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28979918/dcas9-mediated-transcriptional-activation-of-tissue-inhibitor-of-metalloproteinases
#19
Tyler Duellman, Andrea Doll, Xi Chen, Rie Wakamiya, Jay Yang
Selective gene activation with the dCas9 (deactivated clustered regularly interspaced short palindromic repeats [CRISPR] associated protein 9)/CRISPR targeting of a transcriptional activator effector is now well established. However, the optimal targeting of guide RNA (gRNA) for a given gene is largely a matter of trial and error. We explored the optimal targeting site for tissue inhibitor of metalloproteinases (TIMPs) by first screening multiple gRNA target sites using a luciferase-based promoter-reporter system and next confirmed the effective TIMP induction in the mouse motor neuron-like neuron-enriched spinal cord 34 (NSC34) cells...
2017: Metalloproteinases in Medicine
https://www.readbyqxmd.com/read/28978445/lipid-order-degradation-in-autoimmune-demyelination-probed-by-polarized-coherent-raman-microscopy
#20
Paulina Gasecka, Alexandre Jaouen, Fatma-Zohra Bioud, Hilton B de Aguiar, Julien Duboisset, Patrick Ferrand, Herve Rigneault, Naveen K Balla, Franck Debarbieux, Sophie Brasselet
Myelin around axons is currently widely studied by structural analyses and large-scale imaging techniques, with the goal to decipher its critical role in neuronal protection. Although there is strong evidence that in myelin, lipid composition, and lipid membrane morphology are affected during the progression of neurodegenerative diseases, there is no quantitative method yet to report its ultrastructure in tissues at both molecular and macroscopic levels, in conditions potentially compatible with in vivo observations...
October 3, 2017: Biophysical Journal
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