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Excitotoxicity

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https://www.readbyqxmd.com/read/27931744/learning-from-one-s-mistakes-a-dual-role-for-the-rostromedial-tegmental-nucleus-in-the-encoding-and-expression-of-punished-reward-seeking
#1
Peter J Vento, Nathan W Burnham, Courtney S Rowley, Thomas C Jhou
BACKGROUND: Psychiatric disorders such as addiction and mania are marked by persistent reward seeking despite highly negative or aversive outcomes, but the neural mechanisms underlying this aberrant decision making are unknown. The recently identified rostromedial tegmental nucleus (RMTg) encodes a wide variety of aversive stimuli and sends robust inhibitory projections to midbrain dopamine neurons, leading to the hypothesis that the RMTg provides a brake to reward signaling in response to aversive costs...
October 21, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27931151/regulation-of-mitochondrial-function-and-glutamatergic-system-are-the-target-of-guanosine-effect-in-traumatic-brain-injury
#2
Fernando Dobrachinski, Rogério da Rosa Gerbatin, Glaubia Sartori, Naiane Ferreira Marques, Ana Paula Pegoraro Zemolin, Luiz Fernando Almeida Silva, Jeferson Luis Franco, Luiz Fernando Freire Royes, Michele Rechia Fighera, Félix Alexandre Antunes Soares
Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Experimental trauma involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. Mitochondrial dysfunction and glutamatergic excitotoxicity are the most important mechanisms of damage. In order to be successful, pharmacologic intervention requires a multifaceted approach. Guanosine (GUO) is known for its neuromodulator effects in different models of brain pathology, which regulates the glutamatergic system...
December 8, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27928512/extracellular-vesicle-associated-a%C3%AE-mediates-trans-neuronal-bioenergetic-and-ca-2-handling-deficits-in-alzheimer-s-disease-models
#3
Erez Eitan, Emmette R Hutchison, Krisztina Marosi, James Comotto, Maja Mustapic, Saket M Nigam, Caitlin Suire, Chinmoyee Maharana, Gregory A Jicha, Dong Liu, Vasiliki Machairaki, Kenneth W Witwer, Dimitrios Kapogiannis, Mark P Mattson
Alzheimer's Disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs) are small 50-150 nanometer membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient CSF and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca(2+) homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity...
2016: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/27920149/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#4
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in posttranscriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter pathology. However, little is known about their role in grey matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27918874/effects-of-the-natural-%C3%AE-carboline-alkaloid-harmine-a-main-constituent-of-ayahuasca-in-memory-and-in-the-hippocampus-a-systematic-literature-review-of-preclinical-studies
#5
Rafael G Dos Santos, Jaime E C Hallak
Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning...
December 5, 2016: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/27908408/protective-effect-of-magnesium-acetyltaurate-against-nmda-induced-retinal-damage-involves-restoration-of-minerals-and-trace-elements-homeostasis
#6
Azliana Jusnida Ahmad Jafri, Natasha Najwa Nor Arfuzir, Lidawani Lambuk, Igor Iezhitsa, Renu Agarwal, Puneet Agarwal, Norhafiza Razali, Anna Krasilnikova, Maria Kharitonova, Vasily Demidov, Evgeny Serebryansky, Anatoly Skalny, Alexander Spasov, Ahmad Pauzi Md Yusof, Nafeeza Mohd Ismail
Glutamate-mediated excitotoxicity involving N-methyl-d-aspartate (NMDA) receptors has been recognized as a final common outcome in pathological conditions involving death of retinal ganglion cells (RGCs). Overstimulation of NMDA receptors results in influx of calcium (Ca) and sodium (Na) ions and efflux of potassium (K). NMDA receptors are blocked by magnesium (Mg). Such changes due to NMDA overstimulation are also associated with not only the altered levels of minerals but also that of trace elements and redox status...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27904735/urinary-metabolomics-of-young-italian-autistic-children-supports-abnormal-tryptophan-and-purine-metabolism
#7
Federica Gevi, Lello Zolla, Stefano Gabriele, Antonio M Persico
BACKGROUND: Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides a sensitive tool to identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines and plasma of ASD and control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences in technology, ethnicity, age range, and definition of "control" status...
2016: Molecular Autism
https://www.readbyqxmd.com/read/27904472/clearing-the-corpses-regulatory-mechanisms-novel-tools-and-therapeutic-potential-of-harnessing-microglial-phagocytosis-in-the-diseased-brain
#8
REVIEW
Irune Diaz-Aparicio, Sol Beccari, Oihane Abiega, Amanda Sierra
Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27902774/intravenous-treatment-with-a-long-chain-omega-3-lipid-emulsion-provides-neuroprotection-in-a-murine-model-of-ischemic-stroke-a-pilot-study
#9
Dirk Berressem, Konrad Koch, Nicole Franke, Jochen Klein, Gunter P Eckert
Single long-chain omega-3 fatty acids (e.g. docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA)) are known for their neuroprotective properties associated with ischemic stroke. This pilot study aimed to test the effectiveness of an acute treatment with a long-chain omega-3 lipid emulsion (Omegaven 10%®, OGV) that contains fish oil (DHA 18 mg/ml; EPA 21 mg/ml) and α-tocopherol (0.2 mg/ml) in a transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in mice. For this purpose, female CD-1 mice were anesthetized and subjected to 90 minutes of MCAO...
2016: PloS One
https://www.readbyqxmd.com/read/27897242/cortical-synaptic-and-dendritic-spine-abnormalities-in-a-presymptomatic-tdp-43-model-of-amyotrophic-lateral-sclerosis
#10
Matthew J Fogarty, Paul M Klenowski, John D Lee, Joy R Drieberg-Thompson, Selena E Bartlett, Shyuan T Ngo, Massimo A Hilliard, Mark C Bellingham, Peter G Noakes
Layer V pyramidal neurons (LVPNs) within the motor cortex integrate sensory cues and co-ordinate voluntary control of motor output. In amyotrophic lateral sclerosis (ALS) LVPNs and spinal motor neurons degenerate. The pathogenesis of neural degeneration is unknown in ALS; 10% of cases have a genetic cause, whereas 90% are sporadic, with most of the latter showing TDP-43 inclusions. Clinical and experimental evidence implicate excitotoxicity as a prime aetiological candidate. Using patch clamp and dye-filling techniques in brain slices, combined with high-resolution confocal microscopy, we report increased excitatory synaptic inputs and dendritic spine densities in early presymptomatic mice carrying a TDP-43(Q331K) mutation...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895553/glypican-6-enhances-n-methyl-d-aspartate-receptor-function-in-human-induced-pluripotent-stem-cell-derived-neurons
#11
Kaoru Sato, Kanako Takahashi, Yukari Shigemoto-Mogami, Kaori Chujo, Yuko Sekino
The in vitro use of neurons that are differentiated from human induced pluripotent stem cells (hiPSC-neurons) is expected to improve the prediction accuracy of preclinical tests for both screening and safety assessments in drug development. To achieve this goal, hiPSC neurons are required to differentiate into functional neurons that form excitatory networks and stably express N-methyl-D-aspartate receptors (NMDARs). Recent studies have identified some astrocyte-derived factors that are important for the functional maturation of neurons...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27893888/potential-neuroprotective-effects-of-an-lsd1-inhibitor-in-retinal-ganglion-cells-via-p38-mapk-activity
#12
Takayuki Tsutsumi, Keiichiro Iwao, Hideki Hayashi, Tomoko Kirihara, Takahiro Kawaji, Toshihiro Inoue, Shinjiro Hino, Mitsuyoshi Nakao, Hidenobu Tanihara
Purpose: The epigenetic mechanisms associated with ocular neurodegenerative diseases remain unclear. The present study aimed to determine the role of lysine-specific demethylase 1 (LSD1), which represses transcription by removing the methyl group from methylated lysine 4 of histone H3, in retinal ganglion cell (RGC) survival, and to investigate the details of the neuroprotective mechanism of tranylcypromine, a major LSD1 inhibitor. Methods: The authors evaluated whether tranylcypromine contributes to neuronal survival following stress-induced damage using primary cultured rat RGCs and in vivo N-methyl-D-aspartate (NMDA)-induced excitotoxicity...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27893855/inhibition-of-matrix-metalloproteinase-9-enhances-rod-survival-in-the-s334ter-line3-retinitis-pigmentosa-model
#13
Jung-A Shin, Hwa Sun Kim, Andrew Vargas, Wan-Qing Yu, Yun Sung Eom, Cheryl Mae Craft, Eun-Jin Lee
Retinitis Pigmentosa (RP) is one of the most common forms of inherited visual loss with the initial degeneration of rod photoreceptors, followed by a progressive cone photoreceptor deterioration. Coinciding with this visual loss, the extracellular matrix (ECM) is reorganized, which alters matrix metalloproteinase (MMP) activity levels. A potential pathological role of MMPs, MMP-9 in particular, involves an excitotoxicity-mediated physiological response. In the current study, we examine the MMP-9 and MMP-2 expression levels in the rhodopsin S334ter-line3 RP rat model and investigate the impact of treatment with SB-3CT, a specific MMP-9 and MMP-2 inhibitor, on rod cell survival was tested...
2016: PloS One
https://www.readbyqxmd.com/read/27889433/the-protective-effect-of-curcumin-in-olfactory-ensheathing-cells-exposed-to-hypoxia
#14
Roberta Bonfanti, Teresa Musumeci, Cristina Russo, Rosalia Pellitteri
Curcumin, a phytochemical component derived from the rhizomes of Curcuma longa, has shown a great variety of pharmacological activities, such as anti-inflammatory, anti-tumor, anti-depression and anti-oxidant activity. Therefore, in the last years it has been used as a therapeutic agent since it confers protection in different neurodegenerative diseases, cerebral ischemia and excitotoxicity. Olfactory Ensheathing Cells (OECs) are glial cells of the olfactory system. They are able to secrete several neurotrophic growth factors, promote axonal growth and support the remyelination of damaged axons...
November 23, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27885636/glutamine-synthetase-role-in-neurological-disorders
#15
Arumugam R Jayakumar, Michael D Norenberg
Glutamine synthetase (GS) is an ATP-dependent enzyme found in most species that synthesizes glutamine from glutamate and ammonia. In brain, GS is exclusively located in astrocytes where it serves to maintain the glutamate-glutamine cycle, as well as nitrogen metabolism. Changes in the activity of GS, as well as its gene expression, along with excitotoxicity, have been identified in a number of neurological conditions. The literature describing alterations in the activation and gene expression of GS, as well as its involvement in different neurological disorders, however, is incomplete...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885634/dysregulation-of-glutamate-cycling-mediates-methylmercury-induced-neurotoxicity
#16
Megan Culbreth, Michael Aschner
To examine the toxicological implications of glutamate, this chapter will focus specifically on its impact in the brain. More explicitly, it will illustrate the role glutamate plays in mediating methylmercury (MeHg)-induced neurotoxicity. In this chapter, one intends to highlight the processes that occur prior to glutamate-stimulated excitotoxicity and subsequent neurodegeneration. As such, it will emphasize three main routes by which MeHg alters glutamate homeostasis. It is essential to recognize that these effects are not mutually exclusive, and that they synergistically influence glutamate dysregulation...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27883274/impact-of-the-chronic-omega-3-fatty-acids-supplementation-in-hemiparkinsonism-model-induced-by-6-hydroxydopamine-in-rats
#17
Alexandre Sales Barros, Rafael Yuri Gouveia Crispim, Juliana Cavalcante Uchoa, Ricardo Basto Souza, Jonatas Cavalcante Lemos, Gerardo Cristino Filho, Mirna Marques Bezerra, Thales Fontenele Moraes Pinheiro, Silvânia Maria Mendes de Vasconcelos, Danielle Silveira Macêdo, Glauce Socorro de Barros Viana, Lissiana Magna Vasconcelos Aguiar
Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. The neuronal degeneration may result from the convergence of a number of different pathogenic factors, including apoptosis, excitotoxicity and oxidative stress. Many studies emphasize the importance of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in vital processes such as maintenance of the properties of cell membranes and the participation in signal transduction and biodynamic activity of neuronal membranes...
November 24, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27881907/retinal-safety-of-intravitreal-rtpa-in-healthy-rats-and-under-excitotoxic-conditions
#18
Alejandra Daruich, Jérôme Parcq, Kimberley Delaunay, Marie-Christine Naud, Quentin Le Rouzic, Emilie Picard, Patricia Crisanti, Denis Vivien, Marianne Berdugo, Francine Behar-Cohen
PURPOSE: Intravitreal recombinant tissue plasminogen activator (rtPA) is used off-label for the surgical management of submacular hemorrhage, a severe complication of neovascular age-related macular degeneration. rtPA is approved for coronary and cerebral thrombolysis. However, in ischemic stroke rtPA is known to increase excitotoxic neural cell death by interacting with the N-methyl-D-aspartate (NMDA) receptor. We therefore investigated the retinal toxicity of rtPA in healthy rats and in a model of NMDA-induced retinal excitotoxicity...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27866326/the-neuroprotective-peptide-poly-arginine-12-r12-reduces-cell-surface-levels-of-nmda-nr2b-receptor-subunit-in-cortical-neurons-investigation-into-the-involvement-of-endocytic-mechanisms
#19
Gabriella MacDougall, Ryan S Anderton, Adam B Edwards, Neville W Knuckey, Bruno P Meloni
We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection and reduce calcium influx following in vitro excitotoxicity, as well as reduce brain injury in animal stroke models. Using the neuroprotective peptides poly-arginine R12 (R12) and the NR2B9c peptide fused to the arginine-rich carrier peptide TAT (TAT-NR2B9c; also known as NA-1), we investigated the mechanisms whereby poly-arginine and arginine-rich peptides reduce glutamate-induced excitotoxic calcium influx...
November 20, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27860379/behavior-associated-neuronal-activation-after-kainic-acid-induced-hippocampal-neurotoxicity-is-modulated-in-time
#20
Andrea Aguilar-Arredondo, Fernanda López-Hernández, Lizbeth García-Velázquez, Clorinda Arias, Angélica Zepeda
Kainic acid-induced (KA) hippocampal damage leads to neuronal death and further synaptic plasticity. Formation of aberrant as well as of functional connections after such procedure has been documented. However, the impact of such structural plasticity on cell activation along time after damage and in face of a behavioral demand has not been explored. We evaluated if the mRNA and protein levels of plasticity-related protein synaptophysin (Syp and SYP, respectively) and activity-regulated cytoskeleton-associated protein mRNA and protein levels (Arc and Arc, respectively) in the dentate gyrus were differentially modulated in time in response to a spatial-exploratory task after KA-induced hippocampal damage...
November 11, 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
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