Protection against Aβ-mediated rapid disruption of synaptic plasticity and memory by memantine

Klyubin, Igor; Wang, Qinwen; Reed, Miranda N.; Irving, Elaine A.; Upton, Neil; Hofmeister, Jacki; Cleary, James P.; Anwyl, Roger; Rowan, Michael J.

doi:10.1016/j.neurobiolaging.2009.04.005

Cited by 73Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchDementia and Cognitive Impairment Research

Protection against Aβ-mediated rapid disruption of synaptic plasticity and memory by memantine

Klyubin, Igor, Wang, Qinwen, Reed, Miranda N., Irving, Elaine A., Upton, Neil, Hofmeister, Jacki, Cleary, James P., Anwyl, Roger +1 more·2011·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2009.04.005

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Abstract

Soluble amyloid-β protein (Aβ) may cause cognitive impairment in Alzheimer's disease in the absence of significant neurodegeneration. Here, the ability of the NMDA receptor (NMDAR) antagonist memantine to prevent synthetic Aβ-mediated rapid functional deficits in learned behavior and synaptic plasticity was assessed in the rat. In vitro, pretreatment with a clinically relevant, NMDAR blocking concentration of memantine partially inhibited the induction of long-term potentiation (LTP) in the dentate gyrus and prevented further inhibition caused by exposure to Aβ(1-42). Whereas systemic injection with memantine alone inhibited LTP in the CA1 area in vivo, a subthreshold dose partially abrogated the inhibition of LTP by intracerebroventricular soluble Aβ(1-42). Similarly, systemic treatment with memantine alone impaired performance of an operant learning task and a subthreshold dose prevented the Aβ(1-42)-mediated increase in perseveration errors. The acute protection afforded by memantine, albeit in a narrow dose range, against the rapid disruptive effects of soluble Aβ(1-42) on synaptic plasticity and learned behavior strongly implicate NMDAR-dependent reversible dysfunction of synaptic mechanisms in Aβ-mediated cognitive impairment.

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The electrophysiological techniques were applied according to previous reports.
“The electrophysiological techniques were applied according to our previous reports [24, 25].”
From The Rapid Effect of Bisphenol-A on Long-Term Potentiation in Hippocampus Involves Estrogen Receptors and ERK Activation (2017) · cites this paper as [24]

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Background
Potassium 2-(1-hydroxypentyl)-benzoate promotes long-term potentiation in Aβ1–42-injected rats and APP/PS1 transgenic mice
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In Vivo Plasticity at Hippocampal Schaffer Collateral-CA1 Synapses: Replicability of the LTP Response and Pharmacology in the Long-Evans Rat
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“Previous studies have reported that acute treatment with clinically relevant NMDAR blocking doses of memantine attenuated the rapid disruption of hippocampal LTP in vitro and in vivo ([23]), but produced hypolocomotion and ataxia in operant tasks([24-25]).”
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Pharmacological Modulation of Excitotoxicity through the Combined Use of NMDA Receptor Inhibition and Group III mGlu Activation Reduces TMT-Induced Neurodegeneration in the Rat Hippocampus
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“Memantine at these doses attenuated seizure activity [28] and L-DOPA-induced dyskinesia [29] and protected against Aβ-mediated memory impairment [30].”
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The anaesthetic xenon partially restores an amyloid beta-induced impairment in murine hippocampal synaptic plasticity
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Opposite in vivo effects of agents that stimulate or inhibit the glutamate/cysteine exchanger system on the inhibition of hippocampal LTP by Aß
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Neuroprotective strategies for NMDAR-mediated excitotoxicity in Huntington’s Disease
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Neuroimmune Dynamics in Alzheimer’s Disease Progression
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Emerging Therapeutic Strategies in Alzheimer's Disease
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“…to the NMDA antagonism, memantine is reported to decrease Aβ production (Alley et al., 2009; Ray et al., 2009), suppress synaptic dysfunction (Klyubin et al., 2009) and induce protein phosphatase-2A (PP2A)-mediated reduction of tau hyperphosphorylation (Chohan et al., 2006; Martinez-Coria…”
Background
Amyloid-beta fibrils as active contributors to synaptic dysfunction in Alzheimer’s disease
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Telencephalin protects PAJU cells from amyloid beta protein-induced apoptosis by activating the ezrin/radixin/moesin protein family/phosphatidylinositol-3-kinase/protein kinase B pathway
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“Several studies have addressed the mechanisms underlying amyloid beta protein toxicity in different models([18-20]), but no work so far has tried to assess the role of telencephalin in the neurotoxicity caused by amyloid beta protein.”
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Authors: Klyubin, I., Wang, Q., Reed, M. N., Irving, E. A., Upton, N., Hofmeister, J., Cleary, J. P., Anwyl, R., & Rowan, M. J.
Affiliations: Trinity College Dublin (IE)
Ningbo University (CN)
University of Minnesota (US)
GlaxoSmithKline (United Kingdom) (GB)
Minneapolis VA Medical Center (US)
Corresponding author: Rowan, Michael J.
ORCID: Klyubin, Igor
Wang, Qinwen
Reed, Miranda N.
Irving, Elaine A.
Rowan, Michael J.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2011-04
Volume: 32
Issue: 4
Pages: 614-623
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2009.04.005
OpenAlex: W1995718400
Cited by: 69
References: 0
Citations by year: 2026: 1 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 7 · 2014: 6 · 2013: 12 · 2012: 7
FWCI: 3.09
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Funders: GlaxoSmithKline
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: memantine, amyloid-beta, amyloid-beta 42, NMDA receptor antagonism, synaptic plasticity, long-term potentiation, Alzheimer's disease, cognitive impairment, memory, perseveration, dentate gyrus, CA1, operant conditioning, neuroprotection
MeSH terms: Analysis of Variance, Animals, Behavior, Animal, Electrophysiology, Hippocampus, Learning, Male, Memantine, Synapses, Amyloid beta-Peptides, Rats, Sprague-Dawley, Rats, Wistar, Long-Term Potentiation, Neuroprotective Agents, Excitatory Postsynaptic Potentials, Rats

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Protection against Aβ-mediated rapid disruption of synaptic plasticity and memory by memantine

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