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Excitotoxicity

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https://www.readbyqxmd.com/read/29218096/mir-106a-promotes-tumor-growth-migration-and-invasion-by-targeting-bcl2l11-in-human-endometrial-adenocarcinoma
#1
Weichun Tang, Jie Li, Hongbin Liu, Feng Zhou, Manhua Liu
Growing evidence indicates that miR-106a is involved in tumor growth and metastasis of cancers, but the participation of miR-106a in endometrial adenocarcinoma (EC) is not clear. BCL2L11 is a member of the BCL-2 family and is located in the outer membrane of mitochondria, where this protein acts as a key regulator of excitotoxic apoptosis, apoptosis-inducing factor translocation, and mitochondrial depolarization. To identify a novel therapeutic target in EC, we studied the roles of miR-106a in the proliferation, apoptosis, and metastasis of EC...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29216442/lycopene-depresses-glutamate-release-through-inhibition-of-voltage-dependent-ca-sup-2-sup-entry-and-protein-kinase-c-in-rat-cerebrocortical-nerve-terminals
#2
Cheng-Wei Lu, Chi-Feng Hung, Wei-Horng Jean, Tzu-Yu Lin, Shu-Kuei Huang, Su Jane Wang
Lycopene is a natural dietary carotenoid which was reported to exhibit neuroprotective profile. Considering that excitotoxicity and cell death induced by glutamate are involved in many brain disorders, the effect of lycopene on glutamate release in rat cerebrocortical nerve terminals and the possible mechanism involved in such effect was investigated. We observed here that lycopene inhibited 4-aminopyridine (4-AP)-evoked glutamate release and intrasynaptosomal Ca <sup>2+<sup> concentration elevation...
December 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29209207/antiepileptic-and-neuroprotective-effects-of-oleamide-in-rat-striatum-on-kainate-induced-behavioral-seizure-and-excitotoxic-damage-via-calpain-inhibition
#3
Hye Yeon Nam, Eun Jung Na, Eunyoung Lee, Youngjoo Kwon, Hwa-Jung Kim
Oleamide was first known as a sleep-inducing fatty acid amide, and later shown to have wide range of neuropharmacological effects upon different neurochemical systems. However, the effects of oleamide on brain damage have scarcely been studied, and the molecular mechanisms and sites of its action remain elusive. Kainic acid (KA) has been used to produce an epileptic animal model that mimics human temporal lobe epilepsy and to induce calpain-activated excitotoxicity, which occurs in numerous neurodegenerative disorders...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29208536/hek-293-secretome-attenuates-kainic-acid-neurotoxicity-through-insulin-like-growth-factor-phosphatidylinositol-3-kinases-pathway-and-by-temporal-regulation-of-antioxidant-defense-machineries
#4
Chaitra Venugopal, Y S Harish Chandra Prasad, K Shobha, Venkata Bharatkumar Pinnelli, Anandh Dhanushkodi
A major impediment in the success of cell therapy for neurodegenerative diseases is the poor survival of grafted cells in the in vivo milieu, predominantly due to accumulated reactive oxygen species, thus prompting the search for suitable alternatives. Accumulating evidence suggests that the therapeutic potential of transplanted cells is partially attributed to the secretome released by them into the extracellular milieu. Studies that investigated the neuroprotective potential of the secretome attributes to the mere presence of growth factors without addressing other underlying cellular/molecular changes that occur upon post-secretome intervention like re-establishing the host cell's free radical scavenging machineries...
December 2, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29204664/-central-and-peripheral-aspects-of-noise-induced-hearing-loss
#5
REVIEW
D Basta, M Gröschel, A Ernst
Noise is an important socioeconomic problem in industrialized countries. Development of efficient treatment options for the audiological phenomena resulting from noise-induced hearing loss requires in-depth understanding of the underlying damage mechanisms causing peripheral and central nervous changes. Mechanical damage, ischemia and excitotoxicity are mainly responsible for noise-induced cell death and biophysical changes in the cochlea. Auditory synaptopathy is an additional consequence. Besides these cochlear pathologies, noise exposure leads to extensive changes within the central auditory pathway...
December 4, 2017: HNO
https://www.readbyqxmd.com/read/29203179/neurotransmitters-in-the-mediation-of-cerebral-ischemic-injury
#6
REVIEW
Diana Mayor, Michael Tymianski
Under physiological conditions, neurotransmitters shape neuronal networks and control several cellular and synaptic functions. In the mammalian central nervous system (CNS), excitatory and inhibitory neurotransmission are mediated in large part by Glutamate and gamma-aminobutyric acid (GABA), which are excitatory and inhibitory neurotransmitters, respectively. Glutamate and GABA also play crucial roles in neurological disorders such as cerebral ischemia. Glutamate in particular causes excitotoxicity, known as one of the hallmark mechanisms in the pathophysiology of cerebral ischemic injury for more than thirty years...
December 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29202856/sulfosuccinimidyl-oleate-sodium-is-neuroprotective-and-alleviates-stroke-induced-neuroinflammation
#7
Hiramani Dhungana, Mikko T Huuskonen, Merja Jaronen, Sighild Lemarchant, Humair Ali, Velta Keksa-Goldsteine, Gundars Goldsteins, Katja M Kanninen, Jari Koistinaho, Tarja Malm
BACKGROUND: Ischemic stroke is one of the main causes of death and disability worldwide. It is caused by the cessation of cerebral blood flow resulting in the insufficient delivery of glucose and oxygen to the neural tissue. The inflammatory response initiated by ischemic stroke in order to restore tissue homeostasis in the acute phase of stroke contributes to delayed brain damage. METHODS: By using in vitro models of neuroinflammation and in vivo model of permanent middle cerebral artery occlusion, we demonstrate the neuroprotective and anti-inflammatory effects of sulfosuccinimidyl oleate sodium (SSO)...
December 4, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29201361/quercetin-prevents-spinal-motor-neuron-degeneration-induced-by-chronic-excitotoxic-stimulus-by-a-sirtuin-1-dependent-mechanism
#8
Rafael Lazo-Gomez, Ricardo Tapia
Background: Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders. Effective therapeutic strategies are an unmet need for these disorders. Polyphenols, such as quercetin and resveratrol, are plant-derived compounds that activate sirtuins (SIRTs) and have shown promising results in some models of neuronal death, although their effects have been scarcely tested in models of motor neuron degeneration. Methods: In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the rat spinal cord tissue...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29198207/neuroanatomical-changes-in-people-with-high-schizotypy-relationship-to-glutamate-levels
#9
Gemma Modinos, Alice Egerton, Anna McLaughlin, Katrina McMullen, Veena Kumari, David J Lythgoe, Gareth J Barker, André Aleman, Steve C R Williams
BACKGROUND: Cortical glutamatergic dysfunction is thought to be fundamental for psychosis development, and may lead to structural degeneration through excitotoxicity. Glutamate levels have been related to gray matter volume (GMV) alterations in people at ultra-high risk of psychosis, and we previously reported GMV changes in individuals with high schizotypy (HS), which refers to the expression of schizophrenia-like characteristics in healthy people. This study sought to examine whether GMV changes in HS subjects are related to glutamate levels...
December 4, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/29196215/critical-role-for-annexin-a7-in-secondary-brain-injury-mediated-by-its-phosphorylation-after-experimental-intracerebral-hemorrhage-in-rats
#10
Haiying Li, Shankai Liu, Xiaofeng Sun, Junjie Yang, Ziying Yang, Haitao Shen, Xiang Li, Yizhi Liu, Gang Chen
Glutamate excitotoxicity has been implicated in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Synaptosome associated protein 23 (SNAP23) and SNAP25 are respectively participate in presynaptic glutamate release and postsynaptic glutamate receptor (NMDA receptor) trafficking, both of which are essential for glutamate-mediated excitatory toxicity. SNAP23 and SNAP25 exhibit high homology and SNAP23 has been shown to interact with Annexin A7 (ANXA7). This study was to examine the role of ANXA7 in ICH-induced neuronal damage...
December 2, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29194360/the-modulation-of-nmda-and-ampa-kainate-receptors-by-tocotrienol-rich-fraction-and-%C3%AE-tocopherol-in-glutamate-induced-injury-of-primary-astrocytes
#11
Zahra Abedi, Huzwah Khaza'ai, Sharmili Vidyadaran, Mohd Sokhini Abd Mutalib
Astrocytes are known as structural and supporting cells in the central nervous system (CNS). Glutamate, as a main excitatory amino acid neurotransmitter in the mammalian central nervous system, can be excitotoxic, playing a key role in many chronic neurodegenerative diseases. The aim of the current study was to elucidate the potential of vitamin E in protecting glutamate-injured primary astrocytes. Hence, primary astrocytes were isolated from mixed glial cells of C57BL/6 mice by applying the EasySep® Mouse CD11b Positive Selection Kit, cultured in Dulbecco's modified Eagle medium (DMEM) and supplemented with special nutrients...
December 1, 2017: Biomedicines
https://www.readbyqxmd.com/read/29193273/activation-of-caspase-6-and-cleavage-of-caspase-6-substrates-is-an-early-event-in-nmda-receptor-mediated-excitotoxicity
#12
Kimberly D Girling, Marie-Josee Demers, Jean Laine, Shu Zhang, Yu Tian Wang, Rona K Graham
Excitotoxicity, due to overstimulation of N-methyl D-aspartate receptors (NMDARs), has a pivotal role in many neurological disorders. However, NMDAR antagonists often cause side effects, and identifying more druggable therapeutic targets for NMDAR excitotoxicity is an important goal. Activation of caspases is a downstream effect of excitotoxicity that may be critically involved in NMDAR-mediated cell death. Caspase-6 (casp6) in particular has been shown to play a key role in the pathogenesis of stroke, Huntington disease, and Alzheimer disease...
November 29, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29189017/the-dorsomedial-striatum-mediates-pavlovian-appetitive-conditioning-and-food-consumption
#13
Sindy Cole, Andrew D Stone, Gorica D Petrovich
The dorsomedial striatum (DMS) is an important sensorimotor region mediating the acquisition of goal-directed instrumental reward learning and behavioral flexibility. However, whether the DMS also regulates Pavlovian cue-food learning is less clear. The current study used excitotoxic lesions to determine whether the DMS is critical in Pavlovian appetitive learning and behavior, using discriminative conditioning and reversal paradigms. The results showed that DMS lesions transiently retarded cue-food learning and subsequent reversal of this learning...
December 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/29188487/sodium-metabisulfite-effects-on-ionic-currents-and-excitotoxicity
#14
Ming-Chi Lai, Te-Yu Hung, Kao-Min Lin, Pi-Shan Sung, Shyh-Jong Wu, Chih-Sheng Yang, Yi-Jen Wu, Jing-Jane Tsai, Sheng-Nan Wu, Chin-Wei Huang
How sodium metabisulfite (SMB; Na2S2O5), a popular food preservative and antioxidant, interacts with excitable membrane and induces excitotoxicity is incompletely understood. In this study, the patch-clamp technique was used to investigate and record the electrophysiological effect of SMB on electrically excitable HL-1 cardiomyocytes and NSC-34 neurons, as well as its relationship to pilocarpine-induced seizures and neuronal excitotoxicity in rats. We used Western blotting, to analyze sodium channel expression on hippocampi after chronic SMB treatment...
November 29, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29187252/atypical-non-standard-functions-of-the-microtubule-associated-tau-protein
#15
REVIEW
Ioannis Sotiropoulos, Marie-Christine Galas, Joana M Silva, Efthimios Skoulakis, Susanne Wegmann, Mahmoud Bukar Maina, David Blum, Carmen Laura Sayas, Eva-Maria Mandelkow, Eckhard Mandelkow, Maria Grazia Spillantini, Nuno Sousa, Jesus Avila, Miguel Medina, Amrit Mudher, Luc Buee
Since the discovery of the microtubule-associated protein Tau (MAPT) over 40 years ago, most studies have focused on Tau's role in microtubule stability and regulation, as well as on the neuropathological consequences of Tau hyperphosphorylation and aggregation in Alzheimer's disease (AD) brains. In recent years, however, research efforts identified new interaction partners and different sub-cellular localizations for Tau suggesting additional roles beyond its standard function as microtubule regulating protein...
November 29, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29177102/assessment-of-r18-cog1410-and-app96-110-in-excitotoxicity-and-traumatic-brain-injury
#16
Li Shan Chiu, Ryan S Anderton, Jane L Cross, Vince W Clark, Adam B Edwards, Neville W Knuckey, Bruno P Meloni
Cationic arginine-rich and poly-arginine peptides (referred to as CARPs) have potent neuroprotective properties in in vitro excitotoxicity and in vivo models of stroke. Traumatic brain injury (TBI) shares many pathophysiological processes as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide, poly-arginine R18, with the COG1410 and APP96-110 peptides, which have neuroprotective actions following TBI. In an in vitro cortical neuronal glutamic acid excitotoxicity injury model, R18 was highly neuroprotective and reduced neuronal calcium influx, while COG1410 and APP96-110 displayed modest neuroprotection and were less effective at reducing calcium influx...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/29171502/-memantine-from-the-original-brand-to-generics
#17
N V Titova
Memantine is the first clinically available glutamate antagonist, with an antagonist action at the N-methyl-D-aspartate receptors in the brain, for correction of cognitive and behavioral functions in neurodegenerative disorders. Glutamate mediated excitotoxic neuronal damage has been implicated in Alzheimer's disease (AD) and other parkinsonism-related dementias and, therefore, memantine represents a novel mode of action to counteract the glutamate-mediated excitotoxicity. In moderate to severe AD, 20 mg of memantine shows a positive effect on cognition, mood, behavior and the ability to perform activities of daily living...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29171440/brain-derived-neurotropic-factor-and-gabaergic-transmission-in-neurodegeneration-and-neuroregeneration
#18
REVIEW
Jinwook Kim, Sueun Lee, Sohi Kang, Sung-Ho Kim, Jong-Choon Kim, Miyoung Yang, Changjong Moon
Neurotoxicity induced by stress, radiation, chemicals, or metabolic diseases, is commonly associated with excitotoxicity, oxidative stress, and neuroinflammation. The pathological process of neurotoxicity induces neuronal death, interrupts synaptic plasticity in the brain, and is similar to that of diverse neurodegenerative diseases. Animal models of neurotoxicity have revealed that clinical symptoms and brain lesions can recover over time via neuroregenerative processes. Specifically, brain-derived neurotropic factor (BDNF) and gamma-aminobutyric acid (GABA)-ergic transmission are related to both neurodegeneration and neuroregeneration...
October 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29171438/in-vitro-neuroprotective-effects-of-ciliary-neurotrophic-factor-on-dorsal-root-ganglion-neurons-with-glutamate-induced-neurotoxicity
#19
Shu-Yun Wen, Ai-Min Li, Kuan-Qing Mi, Rui-Zheng Wang, Hao Li, Hua-Xiang Liu, Yi Xing
Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase (JAK) 2/activator of transcription 3 (STAT3) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Whether ciliary neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of dorsal root ganglion neurons is poorly understood. In the present study, the in vitro neuroprotective effects of ciliary neurotrophic factor against glutamate-induced excitotoxicity were determined in a primary culture of dorsal root ganglion neurons from Wistar rat embryos at embryonic day 15...
October 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29164084/pretreatment-with-human-chorionic-gonadotropin-protects-the-neonatal-brain-against-the-effects-of-hypoxic-ischemic-injury
#20
Tammy Z Movsas, Rebecca L Weiner, M Banks Greenberg, David M Holtzman, Rafael Galindo
Introduction: Though the human fetus is exposed to placentally derived human chorionic gonadotropin (hCG) throughout gestation, the role of hCG on the fetal brain is unknown. Review of the available literature appears to indicate that groups of women with higher mean levels of hCG during pregnancy tend to have offspring with lower cerebral palsy (CP) risk. Given that newborn cerebral injury often precedes the development of CP, we aimed to determine whether hCG may protect against the neurodegenerative effects of neonatal brain injury...
2017: Frontiers in Pediatrics
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