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https://www.readbyqxmd.com/read/28935671/efa6-regulates-selective-polarised-transport-and-axon-regeneration-from-the-axon-initial-segment
#1
Richard Eva, Hiroaki Koseki, Venkateswarlu Kanamarlapudi, James W Fawcett
Central nervous system (CNS) axons lose their intrinsic ability to regenerate with maturity, whilst peripheral (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their rab11 carriers. We reasoned that exclusion of the contents of rab11 vesicles including integrins might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this using laser axotomy...
September 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28931574/enhanced-nociception-in-angelman-syndrome-model-mice
#2
Eric S McCoy, Bonnie Taylor-Blake, Megumi Aita, Jeremy M Simon, Benjamin D Philpot, Mark J Zylka
Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutation or deletion of the maternal UBE3A allele. The maternal UBE3A allele is expressed in nearly all neurons of the brain and spinal cord, whereas the paternal UBE3A allele is repressed by an extremely long antisense transcript (UBE3A-ATS). Little is known about expression of UBE3A in the peripheral nervous system, where loss of maternal UBE3A might contribute to AS phenotypes. Here we sought to examine maternal and paternal Ube3a expression in dorsal root ganglia (DRG) neurons and to evaluate whether nociceptive responses were affected in AS model mice (global deletion of maternal Ube3a allele; Ube3a(m-/p+) )...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28931335/activation-of-erk-signaling-by-src-family-kinases-sfks-in-drg-neurons-contributes-to-hydrogen-peroxide-h2o2-induced-thermal-hyperalgesia
#3
Ajeet Kumar Singh, Manjula Vinayak
Concomitant generation of reactive oxygen species during tissue inflammation has been recognized as a major factor for development and maintenance of hyperalgesia, out of which H2O2 is the major player. However, molecular mechanism of H2O2 induced hyperalgesia is still obscure. The aim of present study is to analyze the mechanism of H2O2 induced hyperalgesia in rats. Intraplantar injection of H2O2 (5, 10 and 20 µmoles/paw) induced a significant thermal hyperalgesia in the hind paw, confirmed by increased c-Fos activity in dorsal horn of spinal cord...
September 21, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28926622/a-high-mitochondrial-transport-rate-characterizes-cns-neurons-with-high-axonal-regeneration-capacity
#4
Romain Cartoni, Gulcin Pekkurnaz, Chen Wang, Thomas L Schwarz, Zhigang He
Improving axonal transport in the injured and diseased central nervous system has been proposed as a promising strategy to improve neuronal repair. However, the contribution of each cargo to the repair mechanism is unknown. DRG neurons globally increase axonal transport during regeneration. Because the transport of specific cargos after axonal insult has not been examined systematically in a model of enhanced regenerative capacity, it is unknown whether the transport of all cargos would be modulated equally in injured central nervous system neurons...
2017: PloS One
https://www.readbyqxmd.com/read/28924864/a-nociceptive-role-for-integrin-signaling-in-pain-after-mechanical-injury-to-the-spinal-facet-capsular-ligament
#5
Sijia Zhang, Ethan Zhao, Beth A Winkelstein
Integrins modulate chemically-induced nociception in a variety of inflammatory and neuropathic pain models. Yet, the role of integrins in mechanically-induced pain remains undefined, despite its well-known involvement in cell adhesion and mechanotransduction. Excessive spinal facet capsular ligament stretch is a common injury that induces morphological and functional changes in its innervating afferent neurons and can lead to pain. However, the local mechanisms underlying the translation from tissue deformation to pain signaling are unclear, impeding effective treatment...
September 18, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28919807/effect-of-nerve-injury-on-the-number-of-dorsal-root-ganglion-neurons-and-autotomy-behavior-in-adult-bax-deficient-mice
#6
Chuang Lyu, Gong-Wei Lyu, Aurora Martinez, Tie-Jun Sten Shi
BACKGROUND: The proapoptotic molecule BAX, plays an important role in mitochondrial apoptotic pathway. Dorsal root ganglion (DRG) neurons depend on neurotrophic factors for survival at early developmental stages. Withdrawal of neurotrophic factors will induce apoptosis in DRG neurons, but this type of cell death can be delayed or prevented in neonatal Bax knockout (KO) mice. In adult animals, evidence also shows that DRG neurons are less dependent upon neurotrophic factors for survival...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28919433/the-p2x7-receptor-in-dorsal-root-ganglia-is-involved-in-hiv-gp120-associated-neuropathic-pain
#7
Bing Wu, Lichao Peng, Jinyan Xie, Lifang Zou, Qicheng Zhu, Huaide Jiang, Zhihua Yi, Shouyu Wang, Yun Xue, Yun Gao, Guilin Li, Shuangmei Liu, Chunping Zhang, Guodong Li, Shangdong Liang, Huangui Xiong
Human immunodeficiency virus (HIV)-associated neuropathic pain is common, and studies have shown that HIV envelope glycoprotein 120 (gp120) can directly stimulate primary sensory afferent neurons causing hyperalgesia. The P2X7 receptor in the dorsal root ganglia (DRG) is involved in pain transmission and is closely related to the inflammatory and immune response. In this study, we aimed to explore the role of the P2X7 receptor in gp120-induced neuropathic pain using a rat model specific for this type of pain...
September 14, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28915149/bulleyaconitine-a-preferably-reduces-tetrodotoxin-sensitive-sodium-current-in-uninjured-dorsal-root-ganglion-neurons-of-neuropathic-rats-probably-via-inhibition-of-protein-kinase-c
#8
Man-Xiu Xie, Rui-Ping Pang, Jie Yang, Kai-Feng Shen, Jing Xu, Xiong-Xiong Zhong, Shao-Kun Wang, Xiao-Long Zhang, Yan-Qing Liu, Xian-Guo Liu
Oral Bulleyaconitine A (BLA) is effective for treating neuropathic pain in human patients, but the underlying mechanism is poorly understood. Here, we tested whether BLA blocked voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons. Compelling evidence shows that voltage-gated sodium channels are upregulated in uninjured DRG neurons but downregulated in injured ones following peripheral nerve injury. We found that BLA preferably inhibited Na currents in uninjured DRG neurons in neuropathic rats...
July 17, 2017: Pain
https://www.readbyqxmd.com/read/28912677/reversible-axonal-dystrophy-by-calcium-modulation-in-frataxin-deficient-sensory-neurons-of-yg8r-mice
#9
Belén Mollá, Diana C Muñoz-Lasso, Fátima Riveiro, Arantxa Bolinches-Amorós, Federico V Pallardó, Angel Fernandez-Vilata, María de la Iglesia-Vaya, Francesc Palau, Pilar Gonzalez-Cabo
Friedreich's ataxia (FRDA) is a peripheral neuropathy involving a loss of proprioceptive sensory neurons. Studies of biopsies from patients suggest that axonal dysfunction precedes the death of proprioceptive neurons in a dying-back process. We observed that the deficiency of frataxin in sensory neurons of dorsal root ganglia (DRG) of the YG8R mouse model causes the formation of axonal spheroids which retain dysfunctional mitochondria, shows alterations in the cytoskeleton and it produces impairment of axonal transport and autophagic flux...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28904018/dyslipidemia-impairs-mitochondrial-trafficking-and-function-in-sensory-neurons
#10
Amy E Rumora, Stephen I Lentz, Lucy M Hinder, Samuel W Jackson, Andrew Valesano, Gideon E Levinson, Eva L Feldman
Mitochondrial trafficking plays a central role in dorsal root ganglion (DRG) neuronal cell survival and neurotransmission by transporting mitochondria from the neuronal cell body throughout the bundles of DRG axons. In type 2 diabetes (T2DM), dyslipidemia and hyperglycemia damage DRG neurons and induce mitochondrial dysfunction; however, the impact of free fatty acids and glucose on mitochondrial trafficking in DRG neurons remains unknown. To evaluate the impact of free fatty acids compared to hyperglycemia on mitochondrial transport, primary adult mouse DRG neuron cultures were treated with physiologic concentrations of palmitate and glucose and assessed for alterations in mitochondrial trafficking, mitochondrial membrane potential, and mitochondrial bioenergetics...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28901432/effects-of-coadministration-of-low-dose-cannabinoid-type-2-receptor-agonist-and-morphine-on-vanilloid-receptor-1-expression-in-a-rat-model-of-cancer-pain
#11
Mingyue Zhang, Meng Chi, Huichao Zou, Songyu Tian, Zhaodi Zhang, Guonian Wang
Morphine is widely used as an analgesic to treat moderate to severe pain, but chronic morphine use is associated with development of tolerance and dependence, which limits its analgesic efficacy. Our previous research has showed that nonanalgetic dose of a cannabinoid type 2 (CB2) receptor agonist reduced morphine tolerance in cancer pain. A previous study showed the colocalization of CB2 and transient receptor potential vanilloid 1 (TRPV1) in human and rat dorsal root ganglia (DRG) sensory neurons. Whether coadministration of a CB2 receptor agonist and morphine could reduce TRPV1 expression in morphine‑induced antinociception and tolerance in cancer pain is unclear...
September 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900459/protective-effects-of-bogijetong-decoction-and-its-selected-formula-on-neuropathic-insults-in-streptozotocin-induced-diabetic-animals
#12
Ki-Joong Kim, Uk Namgung, Chung Sik Cho
Bogijetong decoction (BGJTD) is a mixture of herbal formulation which is used in the traditional Korean medicine for the treatment of neuropathic pain caused by diabetes. Here, we investigated the regulatory effects of BGJTD and its reconstituted decoction subgroups on the neuropathic responses in streptozotocin- (STZ-) induced diabetic animals. Be decoction (BeD) was formulated by selecting individual herbal components that induced neurite outgrowth most efficiently in each subgroup. BeD induced the neurite outgrowth in DRG neurons most efficiently among decoction subgroups and downregulated the production of TNF-α from the sciatic nerves in STZ-diabetic animals...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28899787/differential-expression-of-ryanodine-receptor-isoforms-after-spinal-cord-injury
#13
Nicolas Pelisch, Cynthia Gomes, Jacqueline M Nally, Jeffrey C Petruska, David P Stirling
Ryanodine receptors (RyRs) are highly conductive intracellular Ca(2+) release channels and are widely expressed in many tissues, including the central nervous system. RyRs have been implicated in intracellular Ca(2+) overload which can drive secondary damage following traumatic injury to the spinal cord (SCI), but the spatiotemporal expression of the three isoforms of RyRs (RyR1-3) after SCI remains unknown. Here, we analyzed the gene and protein expression of RyR isoforms in the murine lumbar dorsal root ganglion (DRG) and the spinal cord lesion site at 1, 2 and 7 d after a mild contusion SCI...
September 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28891864/photosensitization-of-trpa1-and-trpv1-by-7-dehydrocholesterol-implications-for-the-smith-lemli-opitz-syndrome
#14
Alexandru Babes, Cosmin I Ciotu, Tal Hoffmann, Tatjana I Kichko, Tudor Selescu, Cristian Neacsu, Susanne K Sauer, Peter W Reeh, Michael J M Fischer
Loss of function mutations in the enzyme 7-dehydrocholesterol reductase are responsible for the Smith-Lemli-Opitz syndrome, in which 7-dehydrocholesterol (7-DHC) levels are markedly increased in the plasma and tissues of patients. This increase in 7-DHC is probably associated with the painful and itchy photosensitivity reported by the large majority of Smith-Lemli-Opitz syndrome patients. In order to identify the molecular targets involved in the activation and photosensitization of primary afferents by 7-DHC we focused on TRPA1 and TRPV1, two ion channels expressed in nociceptive nerve endings and previously shown to respond to ultraviolet and visible light under pathophysiological circumstances...
September 1, 2017: Pain
https://www.readbyqxmd.com/read/28888226/modulation-of-hippocampal-neuronal-activity-by-so-ochim-tang-gamibang-in-mice-subjected-to-chronic-restraint-stress
#15
Hwa Chul Shin, Jae Ho Lee, Ki Joong Kim, Hyun Jin Shin, Jeong June Choi, Chan Yong Lee, Uk Namgung, In Chul Jung
BACKGROUND: So-ochim-tang-gamibang (SOCG) is a decoction formula which has been used to improve mental activity in traditional Korean medicine. The present study was performed to evaluate whether the treatment of SOCG was involved in activating hippocampal neurons in mice which were subjected to chronic restraint stress (CRS). METHODS: Mice were subjected to CRS for 2 weeks to induce depressive-like behaviors. SOCG was orally administered for the same period. mRNA expression in the hippocampus was analyzed by RT-PCR...
September 9, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28879680/combining-growth-factor-releasing-microspheres-within-aligned-nanofibers-enhances-neurite-outgrowth
#16
Tonya J Whitehead, Christian Oliver C Avila, Harini G Sundararaghavan
Current treatments for peripheral nerve injuries include autografts, the gold standard, and commercially available nerve growth conduits (NGC). Autografts have several drawbacks including donor site morbidity and nerve size mismatch, which lead to incomplete recovery. However, even with these drawbacks, autografts work better then commercially available NGCs that lack sufficient cues to promote complete regeneration. This study evaluated a combination of biomaterial components that can be added to the hollow internal space of a NGC to promote and direct nerve regeneration; specifically, mechanical, chemical, and topographical cues...
September 6, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28877968/action-potential-broadening-in-capsaicin-sensitive-drg-neurons-from-frequency-dependent-reduction-of-kv3-current
#17
Pin Liu, Nathaniel T Blair, Bruce P Bean
Action potential shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the action potentials. Stimulation at 10 Hz for three seconds resulted in an increase in action potential width by an average of 76 ± 7% at 22 °C and by 38 ± 3% at 35 °C. Action potential clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization...
September 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28877649/the-effect-of-hypothermic-and-cryogenic-preservation-on-engineered-neural-tissue
#18
Adam George Edward Day, Kulraj Singh Bhangra, Celia Murray-Dunning, Lara Stevanato, James Phillips
This study explored different approaches to preserve Engineered Neural Tissue (EngNT), a stabilised cellular collagen hydrogel containing columns of aligned Schwann cells for nervous system repair. The ability to preserve EngNT without disrupting cellular and extracellular components and structures is important for clinical translation and commercialisation. Stabilised cellular gels and EngNT constructs were preserved under various conditions and cell survival assessed using live/dead microscopy and metabolic assay...
September 6, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28872725/dorsal-root-ganglion-field-stimulation-prevents-inflammation-and-joint-damage-in-a-rat-model-of-rheumatoid-arthritis
#19
Bin Pan, Zhiyong Zhang, Dongman Chao, Quinn H Hogan
OBJECTIVES: Electrical stimulation of the dorsal root ganglion (DRG), referred to here as ganglionic field stimulation (GFS), is effective in reducing clinical pain, probably by interrupting transmission of afferent impulse trains on sensory neurons as they pass through the DRG. We therefore tested whether efferent impulse trains conveyed by sensory neurons, which contribute to neurogenic inflammation, may also be interrupted by GFS. MATERIALS AND METHODS: Collagen-induced arthritis, a model of clinical rheumatoid arthritis, was initiated in rats concurrently with the insertion of an electrode for GFS at the fourth lumbar DRG...
September 5, 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/28871176/interleukin-17a-is-involved-in-mechanical-hyperalgesia-but-not-in-the-severity-of-murine-antigen-induced-arthritis
#20
Matthias Ebbinghaus, Gabriel Natura, Gisela Segond von Banchet, Susanne Hensellek, Martin Böttcher, Birgit Hoffmann, Firas Subhi Salah, Mieczyslaw Gajda, Thomas Kamradt, Hans-Georg Schaible
Interleukin-17A (IL-17A) is considered an important pro-inflammatory cytokine but its importance in joint diseases such as rheumatoid arthritis (RA) is unclear. It has also been reported that IL-17A may induce pain but it is unclear whether pro-inflammatory and pro-nociceptive effects are linked. Here we studied in wild type (WT) and IL-17A knockout (IL-17AKO) mice inflammation and hyperalgesia in antigen-induced arthritis (AIA). We found that the severity and time course of AIA were indistinguishable in WT and IL-17AKO mice...
September 4, 2017: Scientific Reports
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