keyword
https://read.qxmd.com/read/33261317/roflumilast-a-camp-specific-phosphodiesterase-4-inhibitor-reduces-oxidative-stress-and-improves-synapse-functions-in-human-cortical-neurons-exposed-to-the-excitotoxin-quinolinic-acid
#21
JOURNAL ARTICLE
Abid Bhat, Vanessa Tan, Benjamin Heng, David B Lovejoy, Meena Kishore Sakharkar, Musthafa Mohamed Essa, Saravana Babu Chidambaram, Gilles J Guillemin
The overexpression of phosphodiesterase 4 (PDE4) enzymes is reported in several neurodegenerative diseases. PDE4 depletes cyclic 3'-5' adenosine monophosphate (cAMP) and, in turn, cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF), the key players in cognitive function. The present study was undertaken to investigate the mechanism behind the protective effects of roflumilast (ROF), a cAMP-specific PDE4 inhibitor, against quinolinic acid (QUIN)-induced neurotoxicity using human primary cortical neurons...
December 16, 2020: ACS Chemical Neuroscience
https://read.qxmd.com/read/33013307/the-discovery-and-characterization-of-targeted-perikaryal-specific-brain-lesions-with-excitotoxins
#22
REVIEW
Joseph T Coyle, Robert Schwarcz
The neurotoxic action of glutamic acid was first described by Lucas and Newhouse, who demonstrated neural degeneration in the inner layers of the neonatal mouse retina after systemic treatment with L-glutamate. Olney extended these findings by showing that neuronal degeneration affected other brain structures including neurons within the arcuate nucleus of the hypothalamus and the area postrema, that the lesion spared axons passing through these areas, and that the neurotoxic potency of glutamate analogs correlated with their excitatory potency, resulting in the designation "excitotoxins...
2020: Frontiers in Neuroscience
https://read.qxmd.com/read/32894500/potential-mechanism-of-cellular-uptake-of-the-excitotoxin-quinolinic-acid-in-primary-human-neurons
#23
JOURNAL ARTICLE
Nady Braidy, Hayden Alicajic, David Pow, Jason Smith, Bat-Erdene Jugder, Bruce J Brew, Joseph A Nicolazzo, Gilles J Guillemin
In Alzheimer's disease (AD), excessive amounts of quinolinic acid (QUIN) accumulate within the brain parenchyma and dystrophic neurons. QUIN also regulates glutamate uptake into neurons, which may be due to modulation of Na+ -dependent excitatory amino acid transporters (EAATs). To determine the biological relationships between QUIN and glutamate dysfunction, we first quantified the functionality and kinetics of [3 H]QUIN uptake in primary human neurons using liquid scintillation. We then measured changes in the protein expression of the glutamate transporter EAAT3 and EAAT1b in primary neurons treated with QUIN and the EAAT inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (2,4-PDC) using western blotting and immunohistochemistry...
September 6, 2020: Molecular Neurobiology
https://read.qxmd.com/read/32710594/tryptophan-metabolites-are-associated-with-symptoms-and-nigral-pathology-in-parkinson-s-disease
#24
JOURNAL ARTICLE
Patrick L Heilman, Ernest W Wang, Mechelle M Lewis, Stanislaw Krzyzanowski, Colt D Capan, Amanda R Burmeister, Guangwei Du, Martha L Escobar Galvis, Patrik Brundin, Xuemei Huang, Lena Brundin
BACKGROUND: The objective of this study was to determine whether neurotoxic kynurenine metabolites, induced by inflammation, in plasma and cerebrospinal fluid (CSF) are associated with symptom severity and nigral pathology in Parkinson's disease (PD). METHODS: Clinical and MRI data were obtained from 97 PD and 89 controls. We used ultra-performance liquid chromatography to quantify kynurenine metabolites and high-sensitivity multiplex assays to quantify inflammation in plasma and CSF...
November 2020: Movement Disorders: Official Journal of the Movement Disorder Society
https://read.qxmd.com/read/32453728/behavioral-flexibility-is-associated-with-changes-in-structure-and-function-distributed-across-a-frontal-cortical-network-in-macaques
#25
JOURNAL ARTICLE
Jérôme Sallet, MaryAnn P Noonan, Adam Thomas, Jill X O'Reilly, Jesper Anderson, Georgios K Papageorgiou, Franz X Neubert, Bashir Ahmed, Jackson Smith, Andrew H Bell, Mark J Buckley, Léa Roumazeilles, Steven Cuell, Mark E Walton, Kristine Krug, Rogier B Mars, Matthew F S Rushworth
One of the most influential accounts of central orbitofrontal cortex-that it mediates behavioral flexibility-has been challenged by the finding that discrimination reversal in macaques, the classic test of behavioral flexibility, is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests that the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity, a group of nine macaques were taught discrimination reversal learning tasks, and its impact on gray matter was measured...
May 2020: PLoS Biology
https://read.qxmd.com/read/32335354/application-of-n-methyl-d-aspartate-receptor-nanopore-in-screening-ligand-molecules
#26
JOURNAL ARTICLE
Shu-Peng Li, Yong-Chao Zhang, Fang-Zhou Hu, Tharani Sabaretnam, Gilles J Guillemin, Ai-Hua Zou
N-methyl-D-aspartate receptors (NMDARs) are crucial for excitatory synaptic transmission in the central nervous system. To study NMDARs more accurately and conveniently, we developed a stable NMDAR nanopore in a planar lipid bilayer. Pharmacological properties were validated using the allosteric modulator Ro 25-6981 and antagonist D-2-amino-5-phosphonopentanoic acid (D-APV). The cyanotoxin β-N-methylamino-L-alanine (BMAA) found in fresh water systems is suspected to be associated with the development of neurodegenerative diseases...
August 2020: Bioelectrochemistry
https://read.qxmd.com/read/32171734/retinal-control-of-lens-induced-astigmatism-in-chicks
#27
JOURNAL ARTICLE
Anca-Vanessa Popa, Chea-Su Kee, William K Stell
PURPOSE: Astigmatism is a refractive error due to meridional differences in refractive powers of lens or cornea. The resulting failure to focus image points in a single plane causes blurred vision at all distances. In this study, using an animal model of lens-induced astigmatism, we tested the hypothesis that induced astigmatism is due to processing of astigmatic retinal image information by the brain, which causes distorted growth in the anterior segment via centrifugal neural projections...
May 2020: Experimental Eye Research
https://read.qxmd.com/read/32036791/simvastatin-edaravone-and-dexamethasone-protect-against-kainate-induced-brain-endothelial-cell-damage
#28
JOURNAL ARTICLE
Lilla Barna, Fruzsina R Walter, András Harazin, Alexandra Bocsik, András Kincses, Vilmos Tubak, Katalin Jósvay, Ágnes Zvara, Patricia Campos-Bedolla, Mária A Deli
BACKGROUND: Excitotoxicity is a central pathological pathway in many neurological diseases with blood-brain barrier (BBB) dysfunction. Kainate, an exogenous excitotoxin, induces epilepsy and BBB damage in animal models, but the direct effect of kainate on brain endothelial cells has not been studied in detail. Our aim was to examine the direct effects of kainate on cultured cells of the BBB and to test three anti-inflammatory and antioxidant drugs used in clinical practice, simvastatin, edaravone and dexamethasone, to protect against kainate-induced changes...
February 10, 2020: Fluids and Barriers of the CNS
https://read.qxmd.com/read/31787761/rod-bipolar-cells-dysfunction-occurs-before-ganglion-cells-loss-in-excitotoxin-damaged-mouse-retina
#29
JOURNAL ARTICLE
Yumeng Shen, Xue Luo, Shiliang Liu, Ying Shen, Scott Nawy, Yin Shen
Progressive degeneration of retinal ganglion cells (RGCs) will cause a blinding disease. Most of the study is focusing on the RGCs itself. In this study, we demonstrate a decline of the presynaptic rod bipolar cells (RBCs) response precedes RGCs loss and a decrease of protein kinase Cα (PKCα) protein expression in RBCs dendrites, using whole-cell voltage-clamp, electroretinography (ERG) measurements, immunostaining and co-immunoprecipitation. We present evidence showing that N-methyl D-aspartate receptor subtype 2B (NR2B)/protein interacting with C kinase 1 (PICK1)-dependent degradation of PKCα protein in RBCs contributes to RBCs functional loss...
December 2, 2019: Cell Death & Disease
https://read.qxmd.com/read/31773641/comparing-the-neuroprotective-effects-of-caffeic-acid-in-rat-cortical-slices-and-caenorhabditis-elegans-involvement-of-nrf2-and-skn-1-signaling-pathways
#30
COMPARATIVE STUDY
Aline Colonnello, Gabriela Aguilera-Portillo, Leonardo C Rubio-López, Benjamín Robles-Bañuelos, Edgar Rangel-López, Samaria Cortez-Núñez, Yadira Evaristo-Priego, Alejandro Silva-Palacios, Sonia Galván-Arzate, Rodolfo García-Contreras, Isaac Túnez, Pan Chen, Michael Aschner, Abel Santamaría
Caffeic acid (CA) is a hydroxycinnamic acid derivative and polyphenol with antioxidant and anti-inflammatory activities. The neuroprotective properties of CA still need detailed characterization in different biological models. Here, the antioxidant and neuroprotective effects of CA were compared in in vitro and in vivo neurotoxic models. Biochemical outcomes of cell dysfunction, oxidative damage, and transcriptional regulation were assessed in rat cortical slices, whereas endpoints of physiological stress and motor alterations were characterized in Caenorhabditis elegans (C...
February 2020: Neurotoxicity Research
https://read.qxmd.com/read/31705657/microtubule-dependent-processes-precede-pathological-calcium-influx-in-excitotoxin-induced-axon-degeneration
#31
JOURNAL ARTICLE
Nan Tian, Kelsey A Hanson, Alison J Canty, James C Vickers, Anna E King
Axon degeneration and axonal loss is a feature of neurodegenerative disease and injury and occurs via programmed pathways that are distinct from cell death pathways. While the pathways of axonal loss following axon severing are well described, less is known about axonal loss following other neurodegenerative insults. Here we use primary mouse cortical neuron cultures grown in compartmentalized chambers to investigate the role of calcium in the degeneration of axons that occurs following a somal insult by the excitotoxin kainic acid...
March 2020: Journal of Neurochemistry
https://read.qxmd.com/read/31678113/pyridine-2-3-dicarboxylate-quinolinic-acid-induces-1n4r-tau-amyloid-aggregation-in-vitro-another-evidence-for-the-detrimental-effect-of-the-inescapable-endogenous-neurotoxin
#32
JOURNAL ARTICLE
Sajjad Esmaeili, Nazanin Ghobadi, Vali Akbari, Sajad Moradi, Mohsen Shahlaie, Sirous Ghobadi, Ali Reza Jalalvand, Mojtaba Amani, Reza Khodarahmi
Quinolinic acid (QA) known as a neuro-active metabolite associated with the kynurenine pathway. At high concentrations, QA is often involved in the initiation and development of several human neurologic diseases, like Alzheimer's disease. Because of the QA action as the NMDA receptor, it is considered as a potent excitotoxin in vivo. Since it is probable that different mechanisms are employed by QA, activation of NMDA receptors cannot fully explain the revealed toxicity and it is even believed that there are multiple unknown mechanisms/targets leading to QA cytotoxicity...
January 5, 2020: Chemico-biological Interactions
https://read.qxmd.com/read/31671109/bdnf-nt-3-and-trk-receptor-agonist-monoclonal-antibodies-promote-neuron-survival-neurite-extension-and-synapse-restoration-in-rat-cochlea-ex-vivo-models-relevant-for-hidden-hearing-loss
#33
JOURNAL ARTICLE
Stephanie Szobota, Pranav D Mathur, Sairey Siegel, KristenAnn Black, H Uri Saragovi, Alan C Foster
Neurotrophins and their mimetics are potential treatments for hearing disorders because of their trophic effects on spiral ganglion neurons (SGNs) whose connections to hair cells may be compromised in many forms of hearing loss. Studies in noise or ototoxin-exposed animals have shown that local delivery of NT-3 or BDNF has beneficial effects on SGNs and hearing. We evaluated several TrkB or TrkC monoclonal antibody agonists and small molecules, along with BDNF and NT-3, in rat cochlea ex vivo models. The TrkB agonists BDNF and a monoclonal antibody, M3, had the greatest effects on SGN survival, neurite outgrowth and branching...
2019: PloS One
https://read.qxmd.com/read/31535503/increase-in-hepatic-quinolinic-acid-concentrations-in-alcohol-withdrawn-rats
#34
JOURNAL ARTICLE
Samina Bano, Iffat Ara, Warda Naseem
BACKGROUND: Behavioral associated disturbance involves excitotoxic quinolinate in alcohol withdrawal syndrome in man due to increase availability of tryptophan. In present study we investigated alcoholism related clinical features in relation to tryptophan and 5-HT levels in rat's model. METHODS: Locally bred male Wistar rats, weighing 200-250 g were housed separately into 6 animals/ group with 12 h light: dark cycle at room temp 22±3 °C. They were given diet ad libitum, for three days then alcohol 8% (v/v) was added into the liquid diet...
July 2019: Journal of Ayub Medical College, Abbottabad: JAMC
https://read.qxmd.com/read/31521737/role-of-prefrontal-cortical-5-ht-2a-receptors-and-serotonin-transporter-in-the-behavioral-deficits-in-post-pubertal-rats-following-neonatal-lesion-of-the-ventral-hippocampus
#35
JOURNAL ARTICLE
Satoru Mitazaki, Osamu Nakagawasai, Hiroshi Onogi, Kenya Watanabe, Kohei Takahashi, Koichi Tan-No, Remi Quirion, Lalit K Srivastava, Takeshi Tadano
Neonatal ventral hippocampal-lesioned (NVHL) rats have been shown to display neurochemical and behavioral abnormalities at adulthood, analogous to some of those seen in schizophrenia. Serotonergic neurotransmission is implicated the pathophysiology and treatment of schizophrenia. In this study, we evaluated possible role of serotonergic transmission is the behaviors of NVHL-lesioned rats. Bilateral lesions to the ventral hippocampus (VH) in rat pups were made using the excitotoxin ibotenic acid. We investigated 5-HT2A -receptor and SERT binding sites in cortical and subcortical areas in post-pubertal NVHL and sham-lesioned rats, using quantitative receptor autoradiography...
September 12, 2019: Behavioural Brain Research
https://read.qxmd.com/read/31501497/excitotoxic-neurodegeneration-is-associated-with-a-focal-decrease-in-metabotropic-glutamate-receptor-type-5-availability-an-in-vivo-pet-imaging-study
#36
JOURNAL ARTICLE
Melissa Crabbé, Nina Dirkx, Cindy Casteels, Koen Van Laere
Metabotropic glutamate receptors (mGluRs) have been proposed as promising therapeutic targets to correct the dysregulated glutamate signaling, associated with neurodegenerative pathologies. Of all mGluR subtypes, especially mGluR5 acts as a modulator of glutamate-induced excitotoxicity. To study the behavior of mGluR5 following localized excitotoxicity, we utilised a pharmacological model that portrays exacerbated neuronal glutamate release, mediated by the endogenous excitotoxin quinolinic acid (QA). Using longitudinal positron emission tomography (PET) with [18 F]FPEB, we investigated cerebral changes in mGluR5 following striatal QA-lesioning...
September 9, 2019: Scientific Reports
https://read.qxmd.com/read/31170999/reactive-microglia-and-il1%C3%AE-il-1r1-signaling-mediate-neuroprotection-in-excitotoxin-damaged-mouse-retina
#37
JOURNAL ARTICLE
Levi Todd, Isabella Palazzo, Lilianna Suarez, Xiaoyu Liu, Leo Volkov, Thanh V Hoang, Warren A Campbell, Seth Blackshaw, Ning Quan, Andy J Fischer
BACKGROUND: Microglia and inflammation have context-specific impacts upon neuronal survival in different models of central nervous system (CNS) disease. Herein, we investigate how inflammatory mediators, including microglia, interleukin 1 beta (IL1β), and signaling through interleukin 1 receptor type 1 (IL-1R1), influence the survival of retinal neurons in response to excitotoxic damage. METHODS: Excitotoxic retinal damage was induced via intraocular injections of NMDA...
June 6, 2019: Journal of Neuroinflammation
https://read.qxmd.com/read/30858084/foxp3-plasmid-encapsulated-plga-nanoparticles-attenuate-pain-behavior-in-rats-with-spinal-nerve-ligation
#38
JOURNAL ARTICLE
Juhee Shin, Yuhua Yin, Do Kyung Kim, Sun Yeul Lee, Wonhyung Lee, Joon Won Kang, Dong Woon Kim, Jinpyo Hong
Microglia play a critical role in neuropathic pain. Since upregulated Foxp3 in microglia enhances tissue repair by resolving neuroinflammation in excitotoxin-induced neuronal death, it may attenuate neuropathic pain in a similar manner. Therefore, this study tests whether Foxp3 introduced with poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles (Foxp3 NPs) can alleviate neuropathic pain by inhibiting microglia activity. The prepared Foxp3 NPs had an anti-inflammatory effect on lipopolysaccharide-stimulated BV2 cells in vitro, and localized to spinal microglia in vivo...
March 8, 2019: Nanomedicine: Nanotechnology, Biology, and Medicine
https://read.qxmd.com/read/30826665/high-phthalate-exposure-increased-urinary-concentrations-of-quinolinic-acid-implicated-in-the-pathogenesis-of-neurological-disorders-is-this-a-potential-missing-link
#39
JOURNAL ARTICLE
Feiby L Nassan, Joshua A Gunn, Melissa M Hill, Brent A Coull, Russ Hauser
BACKGROUND: Quinolinic acid (QA), a neuroactive metabolite of the Kynurenine Pathway (KP), is an excitotoxin that is implicated in the pathogenesis of many neurological disorders. KP is the main tryptophan degradation pathway. Phthalates can structurally mimic tryptophan metabolites and diets containing phthalates in rats enhanced the production and excretion of QA. However, there are no human studies that have examined the association between phthalates and QA. OBJECTIVES: Taking advantage of different mesalamine formulations with/without dibutyl phthalate (DBP), we assessed whether DBP from mesalamine (>1000x background) altered the urinary concentrations of QA...
February 22, 2019: Environmental Research
https://read.qxmd.com/read/30664159/sodium-azide-induces-mitochondria%C3%A2-mediated-apoptosis-in-pc12-cells-through-pgc%C3%A2-1%C3%AE-%C3%A2-associated-signaling-pathway
#40
JOURNAL ARTICLE
Yuanyi Zuo, Jun Hu, Xuehua Xu, Xiangting Gao, Yun Wang, Shaohua Zhu
Sodium azide (NaN3), an inhibitor of cytochrome oxidase, induces the release of excitotoxins via an energy impairment and this, in turn, results in neurodegeneration. The present study aimed to investigate the toxic effects NaN3 on apoptosis of PC12 cells and its mechanism of action in peroxisome proliferator‑activated receptor γ co‑activator 1‑α (Pgc‑1α)‑associated signaling pathways. To induce apoptosis, PC12 cells were exposed to NaN3 (0, 5, 10, 20, 40 and 80 mM) for 12, 24, 48 and 72 h...
January 14, 2019: Molecular Medicine Reports
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