Activity-dependent modulation of NMDA receptors by endogenous zinc shapes dendritic function in cortical neurons

Morabito, Annunziato; Zerlaut, Yann; Serraz, Benjamin; Sala, Romain W; Paoletti, Pierre; Rebola, Nelson

doi:10.1016/j.celrep.2022.110415

Cited by 20 publications

(11 citation statements)

References 63 publications

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“…Accumulating evidence highlights the important roles for Zn 2+ and Ca 2+ interactive signaling in several functional contexts that extend from modulating cellular excitability to mediating cellular injury and cell death ( Claiborne et al, 1989 ; Frederickson and Danscher, 1990 ; Li et al, 2001 ; Quinta-Ferreira et al, 2004 ; Huang et al, 2008 ; Ketterman and Li, 2008 ; Liu et al, 2008 ; Hershfinkel et al, 2009 ; Sindreu et al, 2011 ; Khan et al, 2014 ; Vergnano et al, 2014 ; Woodier et al, 2015 ; Ha et al, 2018 ; Levaot and Hershfinkel, 2018 ; Sanford et al, 2019 ; Morabito et al, 2022 ). Ca 2+ dependent Zn 2+ release is well-documented in several studies.…”

Section: Discussionmentioning

confidence: 99%

The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro

Alshawaf

Alnassar

Al‐Mohanna

2023

Front. Cell. Neurosci.

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Recent pharmacological studies demonstrate a role for zinc (Zn2+) in shaping intracellular calcium (Ca2+) dynamics and vice versa in excitable cells including neurons and cardiomyocytes. Herein, we sought to examine the dynamic of intracellular release of Ca2+ and Zn2+ upon modifying excitability of primary rat cortical neurons using electric field stimulation (EFS) in vitro. We show that exposure to EFS with an intensity of 7.69 V/cm induces transient membrane hyperpolarization together with transient elevations in the cytosolic levels of Ca2+ and Zn2+ ions. The EFS-induced hyperpolarization was inhibited by prior treatment of cells with the K+ channel opener diazoxide. Chemical hyperpolarization had no apparent effect on either Ca2+ or Zn2+. The source of EFS-induced rise in Ca2+ and Zn2+ seemed to be intracellular, and that the dynamic inferred of an interplay between Ca2+ and Zn2+ ions, whereby the removal of extracellular Ca2+ augmented the release of intracellular Ca2+ and Zn2+ and caused a stronger and more sustained hyperpolarization. We demonstrate that Zn2+ is released from intracellular vesicles located in the soma, with major co-localizations in the lysosomes and endoplasmic reticulum. These studies further support the use of EFS as a tool to interrogate the kinetics of intracellular ions in response to changing membrane potential in vitro.

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Section: Discussionmentioning

confidence: 99%

The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro

Alshawaf

Alnassar

Al‐Mohanna

2023

Front. Cell. Neurosci.

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“…In the second series of experiments, the AMPAR component of the EPSC was isolated by adding antagonists for NMDAR (APV, 20 µM), Kainate receptors (UBP-302, 10 μ M ), and GABA A receptors (bicuculline, 20 µM). The results are expressed as percentage changes in baseline EPSC amplitude (vehicle), as previously described [ 66 , 67 ].…”

Section: Methodsmentioning

confidence: 99%

NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System

Lemarchant¹,

Sourioux²,

Douce³

et al. 2022

IJMS

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NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that is under preclinical and clinical development for the treatment of neurological disorders. Here, using whole-cell patch-clamp recordings, we demonstrate that NX210c increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and GluN2A-containing N-methyl-D-aspartate receptor (GluN2A-NMDAR)-mediated excitatory postsynaptic currents in the brain. Accordingly, using extracellular field excitatory postsynaptic potential recordings, an enhancement of synaptic transmission was shown in the presence of NX210c in two different neuronal circuits. Furthermore, the modulation of synaptic transmission and GluN2A-NMDAR-driven signaling by NX210c restored memory in mice chronically treated with the NMDAR antagonist phencyclidine. Overall, by promoting glutamatergic receptor-related neurotransmission and signaling, NX210c represents an innovative therapeutic opportunity for patients suffering from CNS disorders, injuries, and states with crippling synaptic dysfunctions.

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“…Preclinical studies have found that the combination of Mg 2+ and opioids can relieve neuropathic pain in diabetic rats by reducing the level of PKA in the PAG and increasing opioid receptor activity, indicating that Mg 2+ can be used as a supplement for the treatment of pain (Rondon et al, 2010 ; Kulik et al, 2021 ). In addition to Mg 2+ , in vitro studies on mouse hippocampal neurons have confirmed that Zn 2+ can selectively block NMDAR-mediated central neuron excitation (Westbrook and Mayer, 1987 ; Choi and Lipton, 1999 ; Morabito et al, 2022 ). Zn 2+ can inhibit NMDAR by high affinity, voltage-independent, and low affinity, voltage-dependent (Fayyazuddin et al, 2000 ; Rachline et al, 2005 ).…”

Section: The Regulation In the Expression And Activation Of Nmdarsmentioning

confidence: 98%

NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain

Liu

Fang

et al. 2022

Front. Cell. Neurosci.

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Peripheral and central sensitizations of the trigeminal nervous system are the main mechanisms to promote the development and maintenance of chronic orofacial pain characterized by allodynia, hyperalgesia, and ectopic pain after trigeminal nerve injury or inflammation. Although the pathomechanisms of chronic orofacial pain are complex and not well known, sufficient clinical and preclinical evidence supports the contribution of the N-methyl-D-aspartate receptors (NMDARs, a subclass of ionotropic glutamate receptors) to the trigeminal nociceptive signal processing pathway under various pathological conditions. NMDARs not only have been implicated as a potential mediator of pain-related neuroplasticity in the peripheral nervous system (PNS) but also mediate excitatory synaptic transmission and synaptic plasticity in the central nervous system (CNS). In this review, we focus on the pivotal roles and mechanisms of NMDARs in the trigeminal nervous system under orofacial neuropathic and inflammatory pain. In particular, we summarize the types, components, and distribution of NMDARs in the trigeminal nervous system. Besides, we discuss the regulatory roles of neuron-nonneuronal cell/neuron-neuron communication mediated by NMDARs in the peripheral mechanisms of chronic orofacial pain following neuropathic injury and inflammation. Furthermore, we review the functional roles and mechanisms of NMDARs in the ascending and descending circuits under orofacial neuropathic and inflammatory pain conditions, which contribute to the central sensitization. These findings are not only relevant to understanding the underlying mechanisms, but also shed new light on the targeted therapy of chronic orofacial pain.

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Activity-dependent modulation of NMDA receptors by endogenous zinc shapes dendritic function in cortical neurons

Cited by 20 publications

References 63 publications

The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro

The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro

NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System

NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain

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