Synaptic NMDA receptor signalling controls R‐type calcium channel recruitment

Feng, Zhendong; Glebov, Oleg O.

doi:10.1111/ejn.15250

Cited by 4 publications

(3 citation statements)

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“…The induction of LTP requires HFS to depolarize the postsynaptic membrane, then activate the NMDARs, open calcium ion channels to allow Ca 2+ influx, and finally trigger LTP 30 . The NMDAR channel is highly permeable to Ca 2+ and is one of the main intracellular calcium ion channels 31,32 . It can be speculated that the open and close status of NMDAR channels would directly affect the induction of LTP.…”

Section: Discussionmentioning

confidence: 99%

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Long‐term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity

Yin,

Zhu,

Liu

et al. 2023

CNS Neurosci Ther

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IntroductionLong‐term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression.AimsThis study aimed to identify changes in hippocampus synaptic plasticity under LSCS.MethodsThe present study simulated the real long‐term space station environment by conducting a 42‐day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch‐clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting.ResultsThe results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (p < 0.05; p < 0.05, respectively). Meanwhile, LTP was significantly impaired (p < 0.0001), and currents in the NMDAR channel were also significantly reduced (p < 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel.ConclusionThese results suggested that LSCS‐induced depressive behaviors by impairing synaptic plasticity in rat hippocampus.

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Section: Discussionmentioning

confidence: 99%

“… 30 The NMDAR channel is highly permeable to Ca 2+ and is one of the main intracellular calcium ion channels. 31 , 32 It can be speculated that the open and close status of NMDAR channels would directly affect the induction of LTP. Thus, we measured the NMDAR channel currents.…”

Section: Discussionmentioning

confidence: 99%

Long‐term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity

Yin,

Zhu,

Liu

et al. 2023

CNS Neurosci Ther

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“…On the other hand, glutamate, one of the major neurotransmitters involved in excitatory pathways, plays an important role in cortical and hippocampal pathways through NMDA receptors ( Nisar et al, 2022 ). NMDA receptor activation allows the influx of calcium ions into postsynaptic neurons and triggers the activation of a pathway important for synaptic plasticity ( Feng and Glebov, 2021 ). However, excessive glutamate release at the synapse causes intracellular Ca2+ overload, increased free radical production, and Aβ formation, leading to neuronal excitotoxicity and subsequent neuronal dysfunction and apoptosis ( Simões et al, 2018 ; Calvo-Rodriguez et al, 2020 ; Goel et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023

Yang,

Wei,

Tian

et al. 2024

Front. Pharmacol.

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BackgroundDonepezil in combination with memantine is a widely used clinical therapy for moderate to severe dementia. However, real-world population data on the long-term safety of donepezil in combination with memantine are incomplete and variable. Therefore, the aim of this study was to analyze the adverse events (AEs) of donepezil in combination with memantine according to US Food and Drug Administration Adverse Event Reporting System (FAERS) data to provide evidence for the safety monitoring of this therapy.MethodsWe retrospectively analyzed reports of AEs associated with the combination of donepezil and memantine from 2004 to 2023 extracted from the FAERS database. Whether there was a significant association between donepezil and memantine combination therapy and AEs was assessed using four disproportionality analysis methods, namely, the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. To further investigate potential safety issues, we also analyzed differences and similarities in the time of onset and incidence of AEs stratified by sex and differences and similarities in the incidence of AEs stratified by age.ResultsOf the 2,400 adverse drug reaction (ADR) reports in which the combination of donepezil and memantine was the primary suspected drug, most of the affected patients were female (54.96%) and older than 65 years of age (79.08%). We identified 22 different system organ classes covering 100 AEs, including some common AEs such as dizziness and electrocardiogram PR prolongation; fall, pleurothotonus and myoclonus were AEs that were not listed on the drug label. Moreover, we obtained 88 reports of AEs in men and 100 reports of AEs in women; somnolence was a common AE in both men and women and was more common in women, whereas pleurothotonus was a more common AE in men. In addition, we analyzed 12 AEs in patients younger than 18 years, 16 in patients between 18 and 65 years, and 113 in patients older than 65 years. The three age groups had distinctive AEs, but lethargy was the common AE among all age groups. Finally, the median time to AE onset was 19 days in all cases. In both men and women, most AEs occurred within a month of starting donepezil plus memantine, but some continued after a year of treatment.ConclusionOur study identified potential and new AEs of donepezil in combination with memantine; some of these AEs were the same as in the specification, and some of the AE signals were not shown in the specification. In addition, there were sex and age differences in some of the AEs. Therefore, our findings may provide valuable insights for further studies on the safety of donepezil and memantine combination therapy, which are expected to contribute to the safe use of this therapy in clinical practice.

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Adaptive control of synaptic plasticity integrates micro- and macroscopic network function

Scott

Frank

2022

Neuropsychopharmacol.

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Synaptic NMDA receptor signalling controls R‐type calcium channel recruitment

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 4 publications

References 34 publications

Long‐term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity

Long‐term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023

Adaptive control of synaptic plasticity integrates micro- and macroscopic network function

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