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Tetrodotoxin

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https://www.readbyqxmd.com/read/28302446/electrophysiological-evidence-of-increased-glycine-receptor-mediated-phasic-and-tonic-inhibition-by-blockade-of-glycine-transporters-in-spinal-superficial-dorsal-horn-neurons-of-adult-mice
#1
Misa Oyama, Seiya Kuraoka, Shun Watanabe, Takashi Iwai, Mitsuo Tanabe
To understand the synaptic and/or extrasynaptic mechanisms underlying pain relief by blockade of glycine transporter subtypes GlyT1 and GlyT2, whole-cell recordings were made from dorsal horn neurons in spinal slices from adult mice, and the effects of NFPS and ALX-1393, selective GlyT1 and GlyT2 inhibitors, respectively, on phasic evoked or miniature glycinergic inhibitory postsynaptic currents (eIPSCs or mIPSCs) were examined. NFPS and ALX-1393 prolonged the decay phase of eIPSCs without affecting their amplitude...
February 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28298301/in-vivo-optogenetic-activation-of-nav1-8-cutaneous-nociceptors-and-their-responses-to-natural-stimuli
#2
Megan L Uhelski, Daniel J Bruce, Philippe Seguela, George L Wilcox, Donald A Simone
Optogenetic methods utilizing expression of the light-sensitive protein channelrhodopsin-2 (ChR2) in neurons have enabled selective activation of specific subtypes or groups of neurons to determine their functions. Using a transgenic mouse model in which neurons natively expressing Nav1.8, a tetrodotoxin-resistant voltage-gated sodium channel, also express the light-gated channel ChR2, we have been able to determine the functional properties of Nav1.8-expressing cutaneous nociceptors of the glabrous skin in vivo...
March 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28271031/enteroendocrine-derived-glucagon-like-peptide-2-controls-intestinal-amino-acid-transport
#3
Jennifer Lee, Jacqueline Koehler, Bernardo Yusta, Jasmine Bahrami, Dianne Matthews, Mahroukh Rafii, Paul B Pencharz, Daniel J Drucker
OBJECTIVE: Glucagon-like peptide-2 (GLP-2) is co-secreted with GLP-1 from gut endocrine cells, and both peptides act as growth factors to expand the surface area of the mucosal epithelium. Notably, GLP-2 also enhances glucose and lipid transport in enterocytes; however, its actions on control of amino acid (AA) transport remain unclear. Here we examined the mechanisms linking gain and loss of GLP-2 receptor (GLP-2R) signaling to control of intestinal amino acid absorption in mice. METHODS: Absorption, transport, and clearance of essential AAs, specifically lysine, were measured in vivo by Liquid Chromatography triple quadrupole Mass Spectrometry (LC-MS/MS) and ex vivo with Ussing chambers using intestinal preparations from Glp2r(+/+) and Glp2r(-/-) mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28263757/profile-differences-in-tetrodotoxin-transfer-to-skin-and-liver-in-the-pufferfish-takifugu-rubripes
#4
Ryohei Tatsuno, Wei Gao, Kotaro Ibi, Tomoka Mine, Kogen Okita, Gregory Naoki Nishihara, Tomohiro Takatani, Osamu Arakawa
Tetrodotoxin (TTX) was intramuscularly administered to nontoxic cultured specimens of the pufferfish Takifugu rubripes to investigate differences in the toxin transfer and accumulation profiles between the skin and liver. Test fish were administered TTX at doses of 30 (Low dose; LD), 100 (Medium dose; MD), and 300 (High dose; HD) μg/individual, respectively. Liquid chromatography/mass spectrometry analysis for TTX revealed that the TTX concentration in both the skin (0.48-1.7 μg/g) and liver (0.43-6.0 μg/g) at 24 h after the toxin administration increased with an increase in the dose...
March 2, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28262835/high-frequency-stimulation-induces-sonic-hedgehog-release-from-hippocampal-neurons
#5
Yujuan Su, Yuan Yuan, Shengjie Feng, Shaorong Ma, Yizheng Wang
Sonic hedgehog (SHH) as a secreted protein is important for neuronal development in the central nervous system (CNS). However, the mechanism about SHH release remains largely unknown. Here, we showed that SHH was expressed mainly in the synaptic vesicles of hippocampus in both young postnatal and adult rats. High, but not low, frequency stimulation, induces SHH release from the neurons. Moreover, removal of extracellular Ca(2+), application of tetrodotoxin (TTX), an inhibitor of voltage-dependent sodium channels, or downregulation of soluble n-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) proteins, all blocked SHH release from the neurons in response to HFS...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28258626/glucose-concentrations-modulate-brain-derived-neurotrophic-factor-responsiveness-of-neurons-in-the-paraventricular-nucleus-of-the-hypothalamus
#6
William McIsaac, Alastair V Ferguson
The hypothalamic paraventricular nucleus (PVN) is critical for normal energy balance and has been shown to contain high levels of both BDNF and TrkB mRNA. Microinjections of BDNF into the PVN increase energy expenditure, suggesting BDNF plays an important role in energy homeostasis through direct actions in this nucleus. The current studies were undertaken to examine the postsynaptic effects of BDNF on the membrane potential of PVN neurons, and to determine if extracellular glucose concentrations modulated these effects...
March 4, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28254884/a-functional-coupling-between-crmp1-and-nav1-7-for-retrograde-propagation-of-semaphorin3a-signaling
#7
Masayuki Yamane, Naoya Yamashita, Tomonobu Hida, Yoshinori Kamiya, Fumio Nakamura, Pappachan Kolattukudy, Yoshio Goshima
Semaphorin3A (Sema3A) is a secreted type of axon guidance molecules that regulates axon wiring through neuropilin-1 (NRP1) and PlexinAs (PlexAs) receptor complex. Sema3A regulates the dendritic branching through a tetrodotoxin (TTX)-sensitive retrograde axonal transport of PlexAs and Tropomyosin-related kinase A (TrkA) complex. We here demonstrate that Nav1.7, a TTX-sensitive Na(+) channel, by coupling with collapsin response mediator protein 1 (CRMP1), mediates the Sema3A-induced retrograde transport. In mouse dorsal root ganglion (DRG) neurons, Sema3A increased co-localization of PlexA4 and TrkA in the growth cones and axons...
March 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28253405/contributions-of-second-and-third-order-retinal-neurons-to-cone-electroretinograms-after-loss-of-rod-function-in-rhodopsin-p347l-transgenic-rabbits
#8
Taro Kominami, Shinji Ueno, Satoshi Okado, Ayami Nakanishi, Mineo Kondo, Hiroko Terasaki
Purpose: To determine the contribution of second- and third-order retinal neurons to the photopic electroretinograms (ERGs) after the degeneration of the rods in rhodopsin P347L transgenic rabbits (Tg). Methods: Four wild-type (WT) rabbits and four Tg rabbits were studied at 18 months of age. The photopic ERGs elicited at stimulus onset and offset were analyzed. To block different retinal pathways, 2-amino-4-phosphonobutyric acid (APB), 6-cyano-7-nitroquinoxaline-2, 3 (1H,4H)-dione (CNQX), tetrodotoxin (TTX), and N-methyl-DL-aspartic acid (NMDA) were injected intravitreally...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28245608/seasonal-changes-in-the-tetrodotoxin-content-of-the-flatworm-planocera-multitentaculata
#9
Riko Yamada, Tadasuke Tsunashima, Mitsuki Takei, Tatsunori Sato, Yoshiki Wajima, Makoto Kawase, Shotaro Oshikiri, Yusuke Kajitani, Keita Kosoba, Hiroyuki Ueda, Koko Abe, Shiro Itoi, Haruo Sugita
Tetrodotoxin (TTX) is a potent neurotoxin that acts specifically on voltage-gated sodium channels on excitable membranes of muscle and nerve tissues. The biosynthetic process for TTX is unclear, although marine bacteria are generally thought to be the primary producers. The marine flatworm Planocera multitentaculata is a known TTX-bearing organism, and is suspected to be a TTX supplier to pufferfish. In this study, flatworm specimens were collected from an intertidal zone in Hayama, Kanagawa, Japan, the TTX content of the flatworm was measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and seasonal changes in TTX content were investigated...
February 25, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28245573/acute-oral-toxicity-of-tetrodotoxin-in-mice-determination-of-lethal-dose-50-ld50-and-no-observed-adverse-effect-level-noael
#10
Paula Abal, M Carmen Louzao, Alvaro Antelo, Mercedes Alvarez, Eva Cagide, Natalia Vilariño, Mercedes R Vieytes, Luis M Botana
Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard...
February 24, 2017: Toxins
https://www.readbyqxmd.com/read/28239845/stimulation-of-na-k-pump-currents-by-epithelial-nicotinic-receptors-in-rat-colon
#11
Sandra Bader, Lena Lottig, Martin Diener
BACKGROUND AND PURPOSE: Acetylcholine-induced epithelial Cl(-) secretion is generally thought to be mediated by epithelial muscarinic receptors and nicotinic receptors on secretomotor neurons. However, recent data showed the expression of nicotinic receptors by intestinal epithelium and the stimulation of Cl(-) secretion by nicotine in the presence of the neurotoxin, tetrodotoxin. In the present study, we aimed to identify the transporters activated by epithelial nicotinic receptors and to clarify their role in cholinergic regulation of intestinal ion transport...
February 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28225079/multiple-sodium-channel-isoforms-mediate-the-pathological-effects-of-pacific-ciguatoxin-1
#12
Marco C Inserra, Mathilde R Israel, Ashlee Caldwell, Joel Castro, Jennifer R Deuis, Andrea M Harrington, Angelo Keramidas, Sonia Garcia-Caraballo, Jessica Maddern, Andelain Erickson, Luke Grundy, Grigori Y Rychkov, Katharina Zimmermann, Richard J Lewis, Stuart M Brierley, Irina Vetter
Human intoxication with the seafood poison ciguatoxin, a dinoflagellate polyether that activates voltage-gated sodium channels (NaV), causes ciguatera, a disease characterised by gastrointestinal and neurological disturbances. We assessed the activity of the most potent congener, Pacific ciguatoxin-1 (P-CTX-1), on NaV1.1-1.9 using imaging and electrophysiological approaches. Although P-CTX-1 is essentially a non-selective NaV toxin and shifted the voltage-dependence of activation to more hyperpolarising potentials at all NaV subtypes, an increase in the inactivation time constant was observed only at NaV1...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28222167/emergence-and-development-of-gut-motility-in-the-chicken-embryo
#13
N R Chevalier, V Fleury, S Dufour, V Proux-Gillardeaux, A Asnacios
The gastrointestinal tract transports the food bolus by peristalsis. Gut motility starts at an early age in the developing embryo, well before it is required for nutrition of the organism. We present a comprehensive kinematic study of the emergence and physiological development of gut motility in all regions of the lower digestive tract of the chicken embryo from embryonic days E5 through E9. We characterized motility emergence time, propagation patterns, speed, frequency and amplitude of peristalsis waves...
2017: PloS One
https://www.readbyqxmd.com/read/28208796/recent%C3%A2-trends%C3%A2-in%C3%A2-marine%C3%A2-phycotoxins%C3%A2-from%C3%A2-australian%C3%A2-coastal%C3%A2-waters
#14
Penelope Ajani, D Tim Harwood, Shauna A Murray
Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the  marine food web, are of growing concern for Australia. These harmful algae pose a threat to  ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest  growing food sectors in the world. With better monitoring, advanced analytical skills and an  increase in microalgal expertise, many phycotoxins have been identified in Australian coastal  waters in recent years...
February 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28193882/neuronal-hyperexcitability-in-a-mouse-model-of-scn8a-epileptic-encephalopathy
#15
Luis F Lopez-Santiago, Yukun Yuan, Jacy L Wagnon, Jacob M Hull, Chad R Frasier, Heather A O'Malley, Miriam H Meisler, Lori L Isom
Patients with early infantile epileptic encephalopathy (EIEE) experience severe seizures and cognitive impairment and are at increased risk for sudden unexpected death in epilepsy (SUDEP). EIEE13 [Online Mendelian Inheritance in Man (OMIM) # 614558] is caused by de novo missense mutations in the voltage-gated sodium channel gene SCN8A Here, we investigated the neuronal phenotype of a mouse model expressing the gain-of-function SCN8A patient mutation, p.Asn1768Asp (Nav1.6-N1768D). Our results revealed regional and neuronal subtype specificity in the effects of the N1768D mutation...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28192153/comparison-of-the-acute-inhibitory-effects-of-tetrodotoxin-ttx-in-rat-and-human-neuronal-networks-for-risk-assessment-purposes
#16
COMPARATIVE STUDY
Emma E J Kasteel, Remco H S Westerink
Tetrodotoxin (TTX) is an extremely toxic marine neurotoxin. TTX inhibits voltage-gated sodium channels, resulting in a potentially lethal inhibition of neurotransmission. Despite numerous intoxications in Asia and Europe, limited (human) toxicological data are available for TTX. Additionally, the degree of interspecies differences for TTX is not well established, hampering the use of available (animal) data for human risk assessment and establishing regulatory limits for TTX concentrations in (shell)fish. We therefore used micro-electrode array (MEA) recordings as an integrated measure of neurotransmission to demonstrate that TTX inhibits neuronal electrical activity in both primary rat cortical cultures and human-induced pluripotent stem cell (hIPSC)-derived iCell(®) neurons in co-culture with hIPSC-derived iCell(®) astrocytes, with IC50 values of 7 and 10nM, respectively...
March 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28191772/human-induced-pluripotent-cell-derived-sensory-neurons-for-fate-commitment-of-bone-marrow-derived-schwann-cells-implications-for-remyelination-therapy
#17
Sa Cai, Lei Han, Qiang Ao, Ying-Shing Chan, Daisy Kwok-Yan Shum
Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins. Continuing culture in maintenance medium resulted in neuronal networks immunopositive for synaptic vesicle markers and vesicular glutamate transporters suggestive of excitatory neurotransmission...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28188663/histamine-facilitates-gabaergic-transmission-in-the-rat-entorhinal-cortex-roles-of-h1-and-h2-receptors-na-permeable-cation-channels-and-inward-rectifier-k-channels
#18
Nicholas I Cilz, Saobo Lei
In the brain, histamine (HA) serves as a neuromodulator and a neurotransmitter released from the tuberomammillary nucleus (TMN). HA is involved in wakefulness, thermoregulation, energy homeostasis, nociception and learning and memory. The medial entorhinal cortex (MEC) receives inputs from the TMN and expresses HA receptors (H1 , H2 , and H3 ). We investigated the effects of HA on GABAergic transmission in the MEC and found that HA significantly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with an EC50 of 1...
February 11, 2017: Hippocampus
https://www.readbyqxmd.com/read/28160390/angiotensin-ii-type-ii-receptors-and-colonic-dysmotility-in-2-4-dinitrofluorobenzenesulfonic-acid-induced-colitis-in-rats
#19
M G Zizzo, M Auteri, A Amato, G Caldara, D Nuzzo, M Di Carlo, R Serio
BACKGROUND: Angiotensin II (Ang II), the main peptide of the renin-angiotensin system (RAS), has been suggested to be involved in inflammatory bowel diseases. Since RAS has emerged as gut motility regulator, and dysmotility is associated with intestinal inflammation, our objective was to investigate in rat 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis the functionality of RAS and its contribution to colonic motor alterations. METHODS: The effects of Ang II on the longitudinal colonic muscular contractility of control and DNBS-treated rats were characterized in vitro...
February 3, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28159808/optogenetic-identification-of-hypothalamic-orexin-neuron-projections-to-paraventricular-spinally-projecting-neurons
#20
Olga Dergacheva, Akihiro Yamanaka, Alan R Schwartz, Vsevolod Y Polotsky, David Mendelowitz
Orexin neurons, and activation of orexin receptors, are generally thought to be sympathoexcitatory; however, the functional connectivity between orexin neurons and a likely sympathetic target, the hypothalamic spinally-projecting neurons (SPNs) in the paraventricular nucleus of the hypothalamus (PVN), has not been established. To test the hypothesis that orexin neurons project directly to SPNs in the PVN, channelrhodopsin-2 (ChR2) was selectively expressed in orexin neurons to enable photoactivation of ChR2-expressing fibers while examining evoked postsynaptic currents in SPNs in rat hypothalamic slices...
February 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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