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https://www.readbyqxmd.com/read/29721353/immunoexcitotoxicity-as-the-central-mechanism-of-etiopathology-and-treatment-of-autism-spectrum-disorders-a-possible-role-of-fluoride-and-aluminum
#1
REVIEW
Anna Strunecka, Russell L Blaylock, Jiri Patocka, Otakar Strunecky
Our review suggests that most autism spectrum disorder (ASD) risk factors are connected, either directly or indirectly, to immunoexcitotoxicity. Chronic brain inflammation is known to enhance the sensitivity of glutamate receptors and interfere with glutamate removal from the extraneuronal space, where it can trigger excitotoxicity over a prolonged period. Neuroscience studies have clearly shown that sequential systemic immune stimulation can activate the brain's immune system, microglia, and astrocytes, and that with initial immune stimulation, there occurs CNS microglial priming...
2018: Surgical Neurology International
https://www.readbyqxmd.com/read/29545615/assessment-of-intrinsic-and-extrinsic-signaling-pathway-in-excitotoxic-retinal-ganglion-cell-death
#2
Berkeley K Fahrenthold, Kimberly A Fernandes, Richard T Libby
Excitotoxicity leads to the activation of a cytotoxic cascade that causes neuronal death. In the retina, retinal ganglion cells (RGCs) die after an excitotoxic insult. Multiple pathways have been proposed to contribute to RGC death after an excitotoxic insult, including TNF signaling, JNK activation, and ER stress. To test the importance of these pathways in RGC death after excitotoxic injury, the excitotoxin N-methyl-D-aspartate (NMDA) was intravitreally injected into mice deficient in components of these pathways...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321522/accelerated-proteomic-visualization-of-individual-predatory-venoms-of-conus-purpurascens-reveals-separately-evolved-predation-evoked-venom-cabals
#3
S W A Himaya, Frank Marí, Richard J Lewis
Cone snail venoms have separately evolved for predation and defense. Despite remarkable inter- and intra-species variability, defined sets of synergistic venom peptides (cabals) are considered essential for prey capture by cone snails. To better understand the role of predatory cabals in cone snails, we used a high-throughput proteomic data mining and visualisation approach. Using this approach, the relationship between the predatory venom peptides from nine C. purpurascens was systematically analysed. Surprisingly, potentially synergistic levels of κ-PVIIA and δ-PVIA were only identified in five of nine specimens...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321175/upregulation-of-gh-but-not-igf1-in-the-hippocampus-of-the-lactating-dam-after-kainic-acid-injury
#4
Elvira C Arellanes-Licea, José Ávila-Mendoza, Elizabeth C Ramírez-Martínez, Eugenia Ramos, Nancy Uribe-González, Carlos Arámburo, Teresa Morales, Maricela Luna
Lactation embodies a natural model of morphological, neurochemical, and functional brain plasticity. In this reproductive stage, the hippocampus of the female is less sensitive to excitotoxins in contrast to nulliparity. Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are known to be neuroprotective in several experimental models of brain lesion. Here, activation of the GH-IGF1 pituitary-brain axis following kainic acid (7.5 mg/kg i.p. KA) lesion was studied in lactating and nulliparous rats. Serum concentrations of GH and IGF1 were uncoupled in lactation...
February 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29124680/the-antiepileptic-drug-levetiracetam-protects-against-quinolinic-acid-induced-toxicity-in-the-rat-striatum
#5
Maricela Dircio-Bautista, Ana Laura Colín-González, Gabriela Aguilera, Marisol Maya-López, Juana Villeda-Hernández, Sonia Galván-Arzate, Esperanza García, Isaac Túnez, Abel Santamaría
Levetiracetam (LVT) is a relatively novel antiepileptic drug (AED) known to act through binding with the synaptic vesicular 2A (SV2A) protein, thus modulating the presynaptic neurotransmitter release. The tryptophan metabolite quinolinic acid (QUIN) acts as an excitotoxin when its brain concentrations reach toxic levels under pathological conditions. Since increased neuronal excitability induced by QUIN recruits degenerative events in the brain, and novel AED is also expected to exert neuroprotective effects in their pharmacological profiles, in this work the effect of LVT (54 mg/kg, i...
November 9, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28973132/ikk%C3%AE-and-mutant-huntingtin-interactions-regulate-the-expression-of-il-34-implications-for-microglial-mediated-neurodegeneration-in-hd
#6
Ali Khoshnan, Adam Sabbaugh, Barbara Calamini, Steven A Marinero, Denise E Dunn, Jung Hyun Yoo, Jan Ko, Donald C Lo, Paul H Patterson
Neuronal interleukin-34 (IL-34) promotes the expansion of microglia in the central nervous system-microglial activation and expansion are in turn implicated in the pathogenesis of Huntington's disease (HD). We thus examined whether the accumulation of an amyloidogenic exon-1 fragment of mutant huntingtin (mHTTx1) modulates the expression of IL-34 in dopaminergic neurons derived from a human embryonic stem cell line. We found that mHTTx1 aggregates induce IL-34 production selectively in post-mitotic neurons...
November 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934119/integrity-of-cerebellar-fastigial-nucleus-intrinsic-neurons-is-critical-for-the-global-ischemic-preconditioning
#7
Eugene V Golanov, Angelique S Regnier-Golanov, Gavin W Britz
Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN) renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon known as preconditioning. We hypothesized that FN may participate in the mechanisms of ischemic preconditioning as a part of the intrinsic neuroprotective mechanism. To explore potential significance of FN neurons in brain ischemic tolerance we lesioned intrinsic FN neurons with excitotoxin ibotenic acid five days before exposure to 20 min four-vessel occlusion (4-VO) global ischemia while analyzing neuronal damage in Cornu Ammoni area 1 (CA1) hippocampal area one week later...
September 21, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28484490/intraluminal-administration-of-resiniferatoxin-protects-against-clostridium-difficile-toxin-a-induced-colitis
#8
Steven R Vigna
Clostridium difficile toxin A is a colonic inflammatory agent that acts partially by activation of TRPV1 (transient receptor potential vanilloid type 1). Resiniferatoxin (RTX) is an excitotoxin that activates TRPV1 at low concentrations and defunctionalizes TRPV1 at high concentrations. RTX at various doses was injected intraluminally into isolated ileal segments in anesthetized rats. After 3 hours, the treated segments were removed and inflammation was assessed. This acute treatment with RTX resulted in biphasic responses: (1) an increase in inflammation similar to that caused by toxin A and capsaicin at low doses of up to 100 ng RTX and (2) no inflammatory effect of RTX at higher doses (1-100 μg), consistent with a defunctionalizing or neurotoxic effect of RTX at high doses...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28407315/drugs-with-antidepressant-properties-affect-tryptophan-metabolites-differently-in-rodent-models-with-depression-like-behavior
#9
Amanda Eskelund, Yan Li, David P Budac, Heidi K Müller, Maria Gulinello, Connie Sanchez, Gregers Wegener
The metabolism of tryptophan through kynurenine and serotonin pathways is linked to depression. Here, effects of different drugs with antidepressant properties (vortioxetine, fluoxetine, and ketamine) on various tryptophan metabolites in different brain regions and plasma were examined using tandem mass spectrometry (LC-MS/MS), in Flinders Sensitive Line rats, a genetic rat model of depression, and its controls: Flinders Sensitive Line and Sprague-Dawley rats. Protein levels of kynurenine pathway enzymes were measured in the brains and livers of these rat strains...
July 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28375145/crystal-structures-of-human-3-hydroxyanthranilate-3-4-dioxygenase-with-native-and-non-native-metals-bound-in-the-active-site
#10
Lakshmi Swarna Mukhi Pidugu, Heather Neu, Tin Lok Wong, Edwin Pozharski, John L Molloy, Sarah L J Michel, Eric A Toth
3-Hydroxyanthranilate 3,4-dioxygenase (3HAO) is an enzyme in the microglial branch of the kynurenine pathway of tryptophan degradation. 3HAO is a non-heme iron-containing, ring-cleaving extradiol dioxygenase that catalyzes the addition of both atoms of O2 to the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3-HANA) to form quinolinic acid (QUIN). QUIN is a highly potent excitotoxin that has been implicated in a number of neurodegenerative conditions, making 3HAO a target for pharmacological downregulation...
April 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28283886/protein-characterization-of-extracellular-microvesicles-exosomes-released-from-cytotoxin-challenged-rat-cerebrocortical-mixed-culture-and-mouse-n2a-cells
#11
Dhwani Kumar, Rachna Manek, Vijaya Raghavan, Kevin K Wang
A number of neuronal and glial proteins were previously found to be released in free-standing soluble form from cultured brain cells into cell-conditioned media. Here, we sought to examine if similar proteins are also contained in neural and astroglial cell-released extracellular microvesicles/exosomes (MV/E). In this study, MV/E were isolated from cell-conditioned media from control and cytotoxin-challenged rat cerebrocortical mixed culture (CTX) and mouse neuroblastoma N2a cells. Cytotoxin challenges included pro-necrosis calcium ionophore A23187, pro-apoptosis staurosporine (STS), and excitotoxin N-methyl-D-aspartate...
March 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/28276430/beta-trace-protein-as-a-new-non-invasive-immunological-marker-for-quinolinic-acid-induced-impaired-blood-brain-barrier-integrity
#12
Andreas Baranyi, Omid Amouzadeh-Ghadikolai, Dirk von Lewinski, Robert J Breitenecker, Tatjana Stojakovic, Winfried März, Christoph Robier, Hans-Bernd Rothenhäusler, Harald Mangge, Andreas Meinitzer
Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208701/excitotoxins-mitochondrial-and-redox-disturbances-in-multiple-sclerosis
#13
REVIEW
Cecilia Rajda, Dániel Pukoli, Zsuzsanna Bende, Zsófia Majláth, László Vécsei
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27986089/the-anti-inflammatory-role-of-extranuclear-apurinic-apyrimidinic-endonuclease-1-redox-effector-factor-1-in-reactive-astrocytes
#14
Hyunjung Baek, Chae Seong Lim, Hee Sun Byun, Hyun Sil Cho, Yu Ran Lee, Yong Sup Shin, Hyun-Woo Kim, Byeong Hwa Jeon, Dong Woon Kim, Jinpyo Hong, Gang Min Hur, Jin Bong Park
Apurinic/apyrimidinic endonuclease 1 (APE1), a ubiquitous multipurpose protein, is also known as redox effector factor-1 (Ref-1). It is involved in DNA repair and redox signaling and, in turn, oxidative stress-induced neurodegeneration. Although previous studies have demonstrated that APE1/Ref-1 functions as a negative regulator of inflammatory response via several mechanisms in neuronal cells, little is known about the roles of APE1/Ref-1 in glial cells. In this study, we found that cytoplasmic APE1/Ref-1 expression was upregulated in reactive astrocytes of the kainic acid- or lipopolysaccharide (LPS)-injected hippocampus...
December 16, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27810933/nmdars-adapt-to-neurotoxic-hiv-protein-tat-downstream-of-a-glun2a-ubiquitin-ligase-signaling-pathway
#15
Matthew V Green, Stanley A Thayer
HIV-associated neurocognitive disorder (HAND) affects approximately half of HIV-infected patients. Infected non-neuronal cells release neurotoxic factors such as the viral protein transactivator of transcription (Tat) that potentiate NMDAR function. NMDARs regulate synaptic changes observed after exposure to HIV proteins, which may underlie cognitive impairment in HAND patients. Here, we used patch-clamp recording to measure NMDAR-mediated currents in rat hippocampal cultures after exposure to Tat. Tat (4-16 h) potentiated NMDA-evoked whole-cell current and increased the NMDAR:AMPAR ratio of evoked EPSCs...
December 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27510585/characterization-of-the-kynurenine-pathway-in-cd8-human-primary-monocyte-derived-dendritic-cells
#16
Nady Braidy, Helene Rossez, Chai K Lim, Bat-Erdene Jugder, Bruce J Brew, Gilles J Guillemin
The kynurenine (KYN) pathway (KP) is a major degradative pathway of the amino acid, L-tryptophan (TRP), that ultimately leads to the anabolism of the essential pyridine nucleotide, nicotinamide adenine dinucleotide. TRP catabolism results in the production of several important metabolites, including the major immune tolerance-inducing metabolite KYN, and the neurotoxin and excitotoxin quinolinic acid. Dendritic cells (DCs) have been shown to mediate immunoregulatory roles that mediated by TRP catabolism. However, characterization of the KP in human DCs has so far only been partly delineated...
November 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27377707/kyna-analogue-szr72-modifies-cfa-induced-dural-inflammation-regarding-expression-of-perk1-2-and-il-1%C3%AE-in-the-rat-trigeminal-ganglion
#17
M Lukács, K Warfvinge, L S Kruse, J Tajti, F Fülöp, J Toldi, L Vécsei, L Edvinsson
BACKGROUND: Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. METHODS: Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA)...
December 2016: Journal of Headache and Pain
https://www.readbyqxmd.com/read/27374158/aberrant-self-grooming-as-early-marker-of-motor-dysfunction-in-a-rat-model-of-huntington-s-disease
#18
Anna Maria Tartaglione, Monica Armida, Rosa Luisa Potenza, Antonella Pezzola, Patrizia Popoli, Gemma Calamandrei
In the study of neurodegenerative diseases, rodent models provide experimentally accessible systems to study multiple pathogenetic aspects. The identification of early and robust behavioural changes is crucial to monitoring disease progression and testing potential therapeutic strategies in animals. Consistent experimental data support the translational value of rodent self-grooming as index of disturbed motor functions and perseverative behaviour patterns in different rodent models of brain disorders. Huntington's disease (HD) is a progressive neurodegenerative disorder, characterized by severe degeneration of basal ganglia, cognitive and psychiatric impairments and motor abnormalities...
October 15, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27179931/a-method-for-objectively-quantifying-propidium-iodide-exclusion-in-organotypic-hippocampal-slice-cultures
#19
Denise F Happ, R Andrew Tasker
BACKGROUND: Organotypic hippocampal slice cultures (OHSCs) are an attractive in vitro model to examine mechanisms of neuronal injury, because the normal hippocampal architecture, function and cellular diversity are mostly preserved. The effects of exposure to excitotoxins such as N-methyl-d-aspartate (NMDA) on cell viability can be determined by propidium iodide (PI) staining. NEW METHOD: We describe a simple method to objectively quantify cell death in NMDA exposed slice cultures using PI that provides a standardized means of quantifying cell death in hippocampal subfields without the need to induce maximal cell death in each slice...
August 30, 2016: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/27053564/lack-of-chronic-histologic-lesions-supportive-of-sublethal-spontaneous-seizures-in-fvb-n-mice
#20
Rebecca A Kohnken, Denise J Schwahn
FVB/N mice with 'space cadet' syndrome are prone to audiogenic seizures and are considered excitotoxic 'sensitive' mice due to the neuronal damage that accompanies seizures. FVB/N mice found dead demonstrate acute neuronal cell death--attributed to a massive seizure episode--within the hippocampus and cerebrocortical laminae. However, the behavioral features of FVB/N mice and numerous studies using excitotoxins to induce seizure activity indicate that this strain experiences multiple sublethal seizures. To assess whether FVB/N mice develop histologically detectable lesions, we evaluated the brains of 86 aged (154-847 d) FVB/N mice without a history of seizures...
April 2016: Comparative Medicine
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