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Concept

Excitotoxicity

Related publications (29)

Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study

Lijing Xin

This study aims to determine whether 1) individuals with treatment-resistant schizophrenia display early cognitive impairment compared to treatment-responders and healthy controls and 2) N-methyl-D-aspartate-receptor hypofunction is an underlying mechanism ...

Springernature2024

Early Neuroprotective Effects of Bovine Lactoferrin Associated with Hypothermia after Neonatal Brain Hypoxia-Ischemia in Rats

Yohan Van de Looij, Analina Raquel Hausin

Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) in term newborns is a leading cause of mortality and chronic disability. Hypothermia (HT) is the only clinically available therapeutic intervention; however, its neuroprotective effects are limited. Lacto ...

MDPI2023

A conditional glutamatergic synaptic vesicle marker for Drosophila

Evelyne Ruchti, Brian Donal McCabe

Glutamate is a principal neurotransmitter used extensively by the nervous systems of all vertebrate and invertebrate animals. It is primarily an excitatory neurotransmitter that has been implicated in nervous system development, as well as a myriad of brai ...

OXFORD UNIV PRESS INC2022

Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state

Anne-Marinette Thi Phuong Hanh Cao

Here, the authors use smFRET to assess the structural dynamics of metabotropic glutamate receptor mGlu2 and show that a positive allosteric modulator or the Gi protein stabilize mGlu2 in the glutamate-induced active state, leading to the full activation of ...

Nature Portfolio2021

Impairment of Glycolysis-Derived L-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer's Disease

Graham Knott

Alteration of brain aerobic glycolysis is often observed early in the course of Alzheimer's disease (AD). Whether and how such metabolic dysregulation contributes to both synaptic plasticity and behavioral deficits in AD is not known. Here, we show that th ...

Cell Press2020

Safinamide inhibits in vivo glutamate release in a rat model of Parkinson's disease

Salvatore Novello

To investigate whether the reversible MAO-B inhibitor and sodium channel blocker safinamide impairs glutamate release under parkinsonian conditions in vivo, and this effect is dependent on MAO-B inhibition, safinamide (and rasagiline as a comparator) were ...

PERGAMON-ELSEVIER SCIENCE LTD2020

A Computational Model of Loss of Dopaminergic Cells in Parkinson's Disease Due to Glutamate-Induced Excitotoxicity

Srikanth Ramaswamy, Vignayanandam Ravindernath Muddapu

Parkinson's disease (PD) is a neurodegenerative disease associated with progressive and inexorable loss of dopaminergic cells in Substantia Nigra pars compacta (SNc). Although many mechanisms have been suggested, a decisive root cause of this cell loss is ...

2019

Magnetic Resonance Spectroscopy in Schizophrenia: Evidence for Glutamatergic Dysfunction and Impaired Energy Metabolism

Lijing Xin, João Miguel das Neves Duarte

In the past couple of decades, major efforts were made to increase reliability of metabolic assessments by magnetic resonance methods. Magnetic resonance spectroscopy (MRS) has been valuable for providing in vivo evidence and investigating biomarkers in ne ...

2019

Dual action of L-Lactate on the activity of NR2B-containing NMDA receptors: from potentiation to neuroprotection

Pierre Magistretti, Pierre Marquet, Igor Allaman, Pascal Jourdain

L-Lactate is a positive modulator of NMDAR-mediated signaling resulting in plasticity gene induction and memory consolidation. However, L-Lactate is also able to protect neurons against excito-toxic NMDAR activity, an indication of a mitigating action of L ...

Nature Research2018

Cannabis use in early psychosis is associated with reduced glutamate levels in the prefrontal cortex

Rolf Gruetter, Lijing Xin

Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressing Glu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (m ...

Springer Verlag2018

Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis

Rolf Gruetter, Lijing Xin, Benoît Schaller, Huanxiang Lu

BACKGROUND: Oxidative stress and glutathione (GSH) metabolism dysregulation has been implicated in the pathophysiology of schizophrenia. GAG-trinucleotide repeat (TNR) polymorphisms in the glutamate-cysteine ligase catalytic gene (GCLC), the rate-limiting ...

Oxford University Press2016

L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

Pierre Magistretti, Pierre Marquet, Igor Allaman, Pascal Jourdain

Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture ...

Nature Research2016

GDH-Dependent Glutamate Oxidation in the Brain Dictates Peripheral Energy Substrate Distribution

Rolf Gruetter

Glucose, the main energy substrate used in the CNS, is continuously supplied by the periphery. Glutamate, the major excitatory neurotransmitter, is foreseen as a complementary energy contributor in the brain. In particular, astrocytes actively take up glut ...

Elsevier2015

Astrocytes: New Targets for the Treatment of Neurodegenerative Diseases

Pierre Magistretti, Sylvain Eric Lengacher, Charles Léonard Finsterwald

The causes of neurodegenerative disorders are multiple, and for most of them a mechanistic understanding is still lacking. However, neurodegenerative diseases such as Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) al ...

Bentham Science Publishers2015

Involvement of autophagy in hypoxic-excitotoxic neuronal death

Neuronal autophagy is increased in numerous excitotoxic conditions including neonatal cerebral hypoxia-ischemia (HI). However, the role of this HI-induced autophagy remains unclear. To clarify this role we established an in vitro model of excitotoxicity co ...

Landes Bioscience2014

Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

Pierre Magistretti, Igor Allaman, Pascal Jourdain, Gabriele Grenningloh, Evelyne Ruchti, Jiangyan Yang

L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism invo ...

National Academy of Sciences2014

The H50Q Mutation Enhances alpha-Synuclein Aggregation, Secretion, and Toxicity

Hilal Lashuel, Giovanni Dietler, Bruno Claude Daniel Fauvet, Francesco Simone Ruggeri, Anne-Laure Mahul Mellier, Abid Oueslati, Martial Mbefo Kamdem, Ossama Mohamed Salah El-Dien El-Sayed Ibrahim Khalaf, Filip Vercruysse

Over the last two decades, the identification of missense mutations in the alpha-synuclein (alpha-Syn) gene SNCA in families with inherited Parkinson disease (PD) has reinforced the central role of alpha-Syn in PD pathogenesis. Recently, a new missense mut ...

American Society for Biochemistry and Molecular Biology2014

Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

Rolf Gruetter, Lijing Xin, Benoît Schaller

Recent studies at high field (7 Tesla) have reported small metabolite changes, in particular lactate and glutamate (below 0.3 μmol/g) during visual stimulation. These studies have been limited to the visual cortex because of its high energy metabolism and ...

Elsevier2014

Net increase of lactate and glutamate concentration in activated human visual cortex detected with magnetic resonance spectroscopy at 7 tesla

Rolf Gruetter, Lijing Xin, Nicolas Kunz, Benoît Schaller

After the landmark studies reporting changes in the cerebral metabolic rate of glucose (CMR(Glc) ) in excess of those in oxygen (CMR(O2) ) during physiological stimulation, several studies have examined the fate of the extra carbon taken up by the brain, r ...

Wiley-Blackwell2013

Characterization of sustained BOLD activation in the rat barrel cortex and Neurochemical consequences

Rolf Gruetter, Lijing Xin, Nathalie Just, Hanne Frenkel

To date, only a couple of functional MR spectroscopy (fMRS) studies were conducted in rats. Due to the low temporal resolution of 1H-MRS techniques, prolonged stimulation paradigms are necessary for investigating the metabolic outcome in the rat brain duri ...

Elsevier2013