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Regulation of the protein complex NEEP21 - GRIP - GluR2 implicated in AMPAR trafficking through endosomal compartments

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Synaptic proximity enables NMDAR signalling to promote brain metastasis

Graham Knott, Douglas Hanahan, Brian Donal McCabe, Iacovos Michael, Mohammad Sadegh Saghafinia, Wei Jiao, Qiqun Zeng

Metastasis-the disseminated growth of tumours in distant organs-underlies cancer mortality. Breast-to-brain metastasis (B2BM) is a common and disruptive form of cancer and is prevalent in the aggressive basal-like subtype, but is also found at varying freq ...

2019

Cortical afferents onto the nucleus Reticularis thalami promote plasticity of low-threshold excitability through GluN2C-NMDARs

Simone Astori

Thalamus and cortex represent a highly integrated processing unit that elaborates sensory representations. Interposed between cortex and thalamus, the nucleus Reticularis thalami (nRt) receives strong cortical glutamatergic input and mediates top-down inhi ...

Nature Research2017

Dual optical control and mechanistic insights into photoswitchable group II and III metabotropic glutamate receptors

Johannes Broichhagen

G protein-coupled receptor (GPCR) signaling occurs in complex spatiotemporal patterns that are difficult to probe using standard pharmacological and genetic approaches. A powerful approach for dissecting GPCRs is to use light-controlled pharmacological age ...

National Academy of Sciences2017

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

Timed Synaptic Inhibition Shapes NMDA Spikes, Influencing Local Dendritic Processing and Global I/O Properties of Cortical Neurons

Henry Markram, Eilif Benjamin Muller, Idan Segev, Giuseppe Chindemi

The NMDA spike is a long-lasting nonlinear phenomenon initiated locally in the dendritic branches of a variety of cortical neurons. It plays a key role in synaptic plasticity and in single-neuron computations. Combining dynamic system theory and computatio ...

2017

GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults

Dimitri Nestor Alice Van De Ville, Maria Giulia Preti

Background: Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregul ...

2019

Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio and myo-inositol concentration in the mouse frontal cortex

João Miguel das Neves Duarte, Rolf Gruetter, Alberto Corcoba

Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects ...

Wiley-Blackwell2017

Image-Based Marker-Free Screening of GABA(A) Agonists, Antagonists, and Modulators

Pierre Marquet, Gerardo Turcatti, Benjamin Rappaz, Pascal Jourdain, Fabien Kuttler, Damiano Banfi

The ionotropic GABA(A) receptors represent the main target for different groups of widely used drugs having hypnotic and anxiolytic effects. So far, most approaches used to assess GABA activity involve invasive low -throughput electrophysiological techniqu ...

2019

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

Subunit-selective N-Methyl-D-aspartate (NMDA) Receptor Signaling through Brefeldin A-resistant Arf Guanine Nucleotide Exchange Factors BRAG1 and BRAG2 during Synapse Maturation

Michael Kintscher

The maturation of glutamatergic synapses in the CNS is regulated by NMDA receptors (NMDARs) that gradually change from a GluN2B- to a GluN2A-dominated subunit composition during postnatal development. Here we show that NMDARs control the activity of the sm ...

Amer Soc Biochemistry Molecular Biology Inc2016

Method for determining cancer invasiveness and patient prognosis

Douglas Hanahan, Leanne Li

A method for determining the prognosis for survival of a patient having cancer is disclosed, said cancer being altered (i.e. highly activated or alternatively inactive/inhibited) in the NMDAR signalling pathway, said method comprising determining the expre ...

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

Single-molecule microscopy to study plasma membrane receptor dynamics

Luc Veya

Cell surface receptors allowthe cell to sense and respond to external signals. Receptor malfunctions are associated with many diseases. The diffusional behavior of receptors is of particular interest to understand how the cell modulates receptor function i ...

EPFL2016

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 dissection of the role of BMP signaling for the development of the auditory brainstem nuclei and the large calyx of Held synapse

Elin Kristina Kronander

Synapses are key elements for communication within the complex network of neurons that make up our brain. Interestingly, synaptic connections can differ greatly in form and function, depending on the specific circuit into which they are embedded. In this P ...

EPFL2016

Amygdala GluN2B-NMDAR dysfunction is critical in abnormal aggression of neurodevelopmental origin induced by St8sia2 deficiency

Maria del Carmen Sandi Perez, Graham Knott, Johannes Gräff, Jocelin Grosse, Olivia Zanoletti, Jose Vicente Sanchez Mut, Catherine Maclachlan, Simone Astori, Wei Tang, Bianca Ambrogina Silva, Elias Georges Gebara, Alexandre Claude Gustave Bacq

Aggression is frequently observed in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and bipolar disorder. Due to a lack of understanding of its underlying mechanisms, effective treatments for abnormal aggression are still missing. ...

2020

Sodium Signaling and Astrocyte Energy Metabolism

Pierre Magistretti

The Na+ gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate the intracellular and extracellular milieu, and discard waste products. One of the most prominent roles of astrocytes in the brain is ...

Wiley-Blackwell2016