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Excitotoxicity

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https://www.readbyqxmd.com/read/28432493/effect-of-pharmacological-modulation-of-activity-of-metabotropic-glutamate-receptors-on-their-gene-expression-after-excitotoxic-damage-in-hippocampal-neurons
#1
E V Pershina, M V Kapralova, V I Arkhipov
Microinjection of kainic acid into rat hippocampus causes excitotoxic neuronal damage predominantly in the CA3 and CA1 fields. These lesions can be significantly reduced by simultaneous administration of MPEP, a negative allosteric modulator of type 5 metabotropic glutamate receptors, and LY354740, an agonist of type 2 metabotropic glutamate receptors. The decrease in neuronal death in the hippocampus during pharmacological modulation was paralleled by adaptive changes in gene expression. In the hippocampus, gene expression of type 5 postsynaptic metabotropic glutamate receptor was close to the control level, and in the frontal cortex expression of the gene of α1-subunit of the GABAA receptor returned to normal...
April 22, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28430183/neuroprotectin-d1-upregulates-iduna-expression-and-provides-protection-in-cellular-uncompensated-oxidative-stress-and-in-experimental-ischemic-stroke
#2
Ludmila Belayev, Pranab K Mukherjee, Veronica Balaszczuk, Jorgelina M Calandria, Andre Obenaus, Larissa Khoutorova, Sung-Ha Hong, Nicolas G Bazan
Ring finger protein 146 (Iduna) facilitates DNA repair and protects against cell death induced by NMDA receptor-mediated glutamate excitotoxicity or by cerebral ischemia. Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator, promotes cell survival under uncompensated oxidative stress (UOS). Our data demonstrate that NPD1 potently upregulates Iduna expression and provides remarkable cell protection against UOS. Iduna, which was increased by the lipid mediator, requires the presence of the poly(ADP-ribose) (PAR) sites...
April 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28424894/the-integrity-of-the-nucleus-of-the-lateral-olfactory-tract-is-essential-for-the-normal-functioning-of-the-olfactory-system
#3
Ricardo P Vaz, Armando Cardoso, Susana I Sá, Pedro A Pereira, M Dulce Madeira
The nucleus of the lateral olfactory tract (nLOT) is a relatively small component of the cortical pallial amygdala, with peculiar neurogenic, neurochemical and connectivity patterns. Although it has been suggested that it might be involved in non-pheromonal olfactory-guided behaviors, particularly feeding, the functional implications of the nLOT have never been investigated. In view of this fact, we have tackled this subject by performing a series of behavioral tests and by quantifying biological and biochemical parameters in sexually naïve adult male rats that were submitted to bilateral excitotoxic lesions of the nLOT...
April 19, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28423185/functional-identification-of-activity-regulated-high-affinity-glutamine-transport-in-hippocampal-neurons-inhibited-by-riluzole
#4
Jeffrey D Erickson
Glutamine (Gln) is considered the preferred precursor for the neurotransmitter pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS. Here, an activity-regulated, high-affinity Gln transport system is described in developing and mature neuron-enriched hippocampal cultures that is potently inhibited by riluzole (IC50 1.3 +/- 0.5μM), an anti-glutamatergic drug, and is blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A transport inhibitor. K(+) -stimulated MeAIB transport displays an affinity (Km ) for MeAIB of 37 +/- 1...
April 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28420961/the-role-of-astrocytes-in-neuroprotection-after-brain-stroke-potential-in-cell-therapy
#5
REVIEW
Andrea Becerra-Calixto, Gloria P Cardona-Gómez
Astrocytes are commonly involved in negative responses through their hyperreactivity and glial scar formation in excitotoxic and/or mechanical injuries. But, astrocytes are also specialized glial cells of the nervous system that perform multiple homeostatic functions for the survival and maintenance of the neurovascular unit. Astrocytes have neuroprotective, angiogenic, immunomodulatory, neurogenic, and antioxidant properties and modulate synaptic function. This makes them excellent candidates as a source of neuroprotection and neurorestoration in tissues affected by ischemia/reperfusion, when some of their deregulated genes can be controlled...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28417216/pathogenic-mechanisms-following-ischemic-stroke
#6
REVIEW
Seyed Esmaeil Khoshnam, William Winlow, Maryam Farzaneh, Yaghoob Farbood, Hadi Fathi Moghaddam
Stroke is the second most common cause of death and the leading cause of disability worldwide. Brain injury following stroke results from a complex series of pathophysiological events including excitotoxicity, oxidative and nitrative stress, inflammation, and apoptosis. Moreover, there is a mechanistic link between brain ischemia, innate and adaptive immune cells, intracranial atherosclerosis, and also the gut microbiota in modifying the cerebral responses to ischemic insult. There are very few treatments for stroke injuries, partly owing to an incomplete understanding of the diverse cellular and molecular changes that occur following ischemic stroke and that are responsible for neuronal death...
April 17, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28411272/disconnection-of-the-perirhinal-and-postrhinal-cortices-impairs-recognition-of-objects-in-context-but-not-contextual-fear-conditioning
#7
Victoria R Heimer-McGinn, D L Poeta, K Aghi, M Udawatta, R D Burwell
The perirhinal cortex (PER) is known to process object information, whereas the rodent postrhinal cortex (POR), homolog to the parahippocampal cortex (PHC) in primates, is thought to process spatial information. A number of studies, however, provide evidence that both areas are involved in processing contextual information. In this study, we tested the hypothesis that the rat POR relies on object information received from the PER to form complex representations of context. Using three fear conditioning paradigms (signaled, unsignaled, and renewal) and two context-guided object recognition tasks (with 3-dimensional and 2-dimensional objects), we examined the effects of crossed excitotoxic lesions to the POR and the contralateral PER...
April 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28400813/adenyl-cyclase-activator-forskolin-protects-against-huntington-s-disease-like-neurodegenerative-disorders
#8
Sidharth Mehan, Shaba Parveen, Sanjeev Kalra
Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington's disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination (grip strength, beam crossing task, locomotor activity), resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus...
February 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28400790/current-view-and-perspectives-in-amyotrophic-lateral-sclerosis
#9
REVIEW
Stéphane Mathis, Philippe Couratier, Adrien Julian, Philippe Corcia, Gwendal Le Masson
Amyotrophic lateral sclerosis (ALS), identified as a distinct clinical entity by Charcot since the end of the nineteenth century, is a devastating and fatal neurodegenerative disorder that affects motor neurons in the brain, brainstem and spinal cord. Survival of patients with ALS is associated with several factors such as clinical phenotype, age at onset, gender, early presence of respiratory failure, weight loss and treatment with Riluzole (the only disease-modifying drug approved for this disease). Nowadays, there is still no curative treatment for ALS: palliative care and symptomatic treatment are therefore essential components in the management of these patients...
February 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28400058/the-snk-and-spar-signaling-pathway-changes-in-hippocampal-neurons-treated-with-amyloid-beta-peptide-in-vitro
#10
Hua Sui, Libin Zhan, Xinping Niu, Lina Liang, Xin Li
Amyloid-β peptide (Aβ) is believed to be a primary cause of Alzheimer's disease. Many studies have demonstrated that Aβ causes morphological and functional alterations of dendritic spines, leading to synaptic dysfunction, but the effect of Aβ on damage to synaptic functions is not fully understood. Spine-associated Rap guanosine triphosphatase-activating protein (SPAR) is an important regulator of activity-dependent remodeling of synapses and is critically involved in both mature dendritic spine formation and the maintenance of spine maturity...
March 22, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28398653/the-noble-gas-xenon-provides-protection-and-trophic-stimulation-to-midbrain-dopamine-neurons
#11
Jérémie Lavaur, Déborah Le Nogue, Marc Lemaire, Jan Pype, Géraldine Farjot, Etienne C Hirsch, Patrick P Michel
Despite its low chemical reactivity, the noble gas xenon possesses a remarkable spectrum of biological effects. In particular, xenon is a strong neuroprotectant in preclinical models of hypoxic-ischemic brain injury. In the present study, we wished to determine whether xenon retained its neuroprotective potential in experimental settings that model the progressive loss of midbrain dopamine (DA) neurons in Parkinson's disease (PD). Using rat midbrain cultures, we established that xenon was partially protective for DA neurons through either direct or indirect effects on these neurons...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28397096/evaluating-a-gene-environment-interaction-in-amyotrophic-lateral-sclerosis-methylmercury-exposure-and-mutated-sod1
#12
REVIEW
Jordan M Bailey, Alexandra Colón-Rodríguez, William D Atchison
PURPOSE OF REVIEW: Gene-environment (GxE) interactions likely contribute to numerous diseases, but are often difficult to model in the laboratory. Such interactions have been widely hypothesized for amyotrophic lateral sclerosis (ALS); recent controlled laboratory studies are discussed here and hypotheses related to possible mechanisms of action are offered. Using methylmercury exposure and mutated SOD1 to model the impacts of such an interaction, we interpret evidence about their respective mechanisms of toxicity to interrogate the possibility of additive (or synergistic) effects when combined...
April 10, 2017: Current Environmental Health Reports
https://www.readbyqxmd.com/read/28396143/lethal-effects-of-an-insecticidal-spider-venom-peptide-involve-positive-allosteric-modulation-of-insect-nicotinic-acetylcholine-receptors
#13
Monique J Windley, Irina Vetter, Richard J Lewis, Graham M Nicholson
κ-Hexatoxins (κ-HXTXs) are a family of excitotoxic insect-selective neurotoxins from Australian funnel-web spiders that are lethal to a wide range of insects, but display no toxicity towards vertebrates. The prototypic κ-HXTX-Hv1c selectively blocks native and expressed cockroach large-conductance calcium-activated potassium (BKCa or KCa1.1) channels, but not their mammalian orthologs. Despite this potent and selective action on insect KCa1.1 channels, we found that the classical KCa1.1 blockers paxilline, charybdotoxin and iberiotoxin, which all block insect KCa1...
April 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28392146/a-small-molecule-inhibitor-of-bax-and-bak-oligomerization-prevents-genotoxic-cell-death-and-promotes-neuroprotection
#14
Xin Niu, Hetal Brahmbhatt, Philipp Mergenthaler, Zhi Zhang, Jing Sang, Michael Daude, Fabian G R Ehlert, Wibke E Diederich, Eve Wong, Weijia Zhu, Justin Pogmore, Jyoti P Nandy, Maragani Satyanarayana, Ravi K Jimmidi, Prabhat Arya, Brian Leber, Jialing Lin, Carsten Culmsee, Jing Yi, David W Andrews
Aberrant apoptosis can lead to acute or chronic degenerative diseases. Mitochondrial outer membrane permeabilization (MOMP) triggered by the oligomerization of the Bcl-2 family proteins Bax/Bak is an irreversible step leading to execution of apoptosis. Here, we describe the discovery of small-molecule inhibitors of Bax/Bak oligomerization that prevent MOMP. We demonstrate that these molecules disrupt multiple, but not all, interactions between Bax dimer interfaces thereby interfering with the formation of higher-order oligomers in the MOM, but not recruitment of Bax to the MOM...
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28391013/p35-hemizygosity-activates-akt-but-does-not-improve-motor-function-in-the-yac128-mouse-model-of-huntington-s-disease
#15
Kevin H J Park, Sonia Franciosi, Kristina Parrant, Ge Lu, Blair R Leavitt
Huntington's disease (HD) is a hereditary neurodegenerative disorder resulting from N-terminal polyglutamine expansion in the huntingtin protein. A relatively selective and early loss of medium spiny neurons in the striatum is a hallmark of HD neuropathology. Although the exact mechanism of mutant huntingtin-mediated neurodegeneration is unclear, recent evidence suggests that NMDA-receptor-mediated excitotoxicity is involved. Our previously published findings show that decreasing levels of the cdk5 activators, p35 and p25, reduces NMDA receptor-mediated excitotoxicity in striatal neurons in vivo...
April 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28386767/increased-quinolinic-acid-in-peripheral-mononuclear-cells-in-alzheimer-s-dementia
#16
Mandy Busse, Vanessa Hettler, Victoria Fischer, Christian Mawrin, Roland Hartig, Henrik Dobrowolny, Bernhard Bogerts, Thomas Frodl, Stefan Busse
The role of monocytes and macrophages in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) is poorly understood. Recently, we have shown that the number of CD14+ monocytes remained constant during healthy aging and in AD patients. Although only little is known about the function of activated macrophages and microglia in AD, one important mechanism involves the expression of quinolinic acid (QUIN), an endogenous N-methyl-D-aspartate glutamate receptor (NMDA-R) agonist which mediates excitotoxicity especially in the hippocampus...
April 6, 2017: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28379489/new-thrombolytic-strategy-providing-neuroprotection-in-experimental-ischemic-stroke-mmp10-alone-or-in-combination-with-tpa
#17
C Roncal, S Martinez de Lizarrondo, A Salicio, A Chevilley, J A Rodriguez, A Rosell, P O Couraud, B Weksler, J Montaner, D Vivien, J A Páramo, J Orbe
Aim: Considering that MMP-10 improves stroke injury, we have examined the therapeutic and protective effect of MMP10 and tPA/MMP10 as clot-dissolving and neuroprotective agent in an experimental model of ischemic stroke and studied in vitro the molecular pathways involved in MMP10-mediated effects. Methods and Results: Cerebral ischemia was induced by the local injection of thrombin into the middle cerebral artery followed by reperfusion with MMP10 (6.5µg/Kg) and tPA (10mg/Kg) alone or in combination with MMP10...
April 3, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28378203/bidirectional-regulation-over-the-development-and-expression-of-loss-of-control-over-cocaine-intake-by-the-anterior-insula
#18
Jean-Yves Rotge, Paul J Cocker, Marie-Laure Daniel, Aude Belin-Rauscent, Barry J Everitt, David Belin
RATIONALE: Increasing evidence suggests that the anterior insular cortex (AIC) plays a major role in cocaine addiction, being implicated in both impaired insight and associated decision-making and also craving and relapse. However, the nature of the involvement of the insula in the development and maintenance of cocaine addiction remains unknown, thereby limiting our understanding of its causal role in addiction. We therefore investigated whether pre- and post-training bilateral lesions of the AIC differentially influenced the development and the expression of the escalation of cocaine self-administration during extended access to the drug...
April 5, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28377703/lesions-of-the-orbitofrontal-but-not-medial-prefrontal-cortex-affect-cognitive-judgment-bias-in-rats
#19
Joanna Golebiowska, Rafal Rygula
Neuroimaging studies in humans have recently shown that the prefrontal cortex (PFC) and orbitofrontal cortex (OFC) mediate bias in the judgment of forthcoming events. In the present study, we sought to determine whether cognitive judgment bias (CJB) is also dependent on these prefrontal regions in non-human animals. For this, we trained a cohort of rats in the ambiguous-cue interpretation (ACI) paradigm, subjected them to excitotoxic lesions in the medial PFC (mPFC) and OFC, and tested the effects of neuronal loss within these regions on CJB...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28377696/als-pathogenesis-and-therapeutic-approaches-the-role-of-mesenchymal-stem-cells-and-extracellular-vesicles
#20
REVIEW
Roberta Bonafede, Raffaella Mariotti
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients...
2017: Frontiers in Cellular Neuroscience
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