Age dependent changes in synaptic NMDA receptor composition in adult human cortical neurons
Age dependent changes in synaptic NMDA receptor composition in adult human cortical neurons
The molecular processes underlying the aging-related decline in cognitive performance and memory observed in humans are poorly understood. Studies in rodents have shown a decrease in N-methyl-D-aspartate receptors (NMDARs) that contain the GluN2B subunit in aging synapses, and this decrease is correlated with impaired memory functions. However, the age-dependent contribution of GluN2B-containing receptors to synaptic transmission in human cortical synapses has not been previously studied. We investigated the synaptic contribution of GluN2A and GluN2B-containing NMDARs in adult human neurons using fresh nonpathological temporal cortical tissue resected during neurosurgical procedures. The tissue we obtained fulfilled quality criteria by the absence of inflammation markers and proteomic degradation. We show an age-dependent decline in the NMDA/AMPA receptor ratio in adult human temporal cortical synapses. We demonstrate that GluN2B-containing NMDA receptors contribute to synaptic responses in the adult human brain with a reduced contribution in older individuals. With previous evidence demonstrating the critical role of synaptic GluN2B in regulating synaptic strength and memory storage in mice, this progressive reduction of GluN2B in the human brain during aging may underlie a molecular mechanism in the age-related decline in cognitive abilities and memory observed in humans.
NR2A, NR2B, human, resected, surgical
4246-4256
Vargas-Caballero, Mariana
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Pegasiou, Chrysia-Maria
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Zolnourian, Ardalan
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Gomez-Nicola, Diego
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Deinhardt, Katrin
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Nicoll, James
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Ahmed, Aminul
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Vajramani, Girish V.
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Grundy, Paul
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Verhoog, Matthijs
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Mansvelder, Huibert
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Perry, V. Hugh
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Bulters, Diederik
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7 July 2020
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Pegasiou, Chrysia-Maria
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Zolnourian, Ardalan
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Gomez-Nicola, Diego
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Deinhardt, Katrin
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Nicoll, James
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Ahmed, Aminul
175a1358-5255-4f20-8cf9-96fac237bc9f
Vajramani, Girish V.
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Grundy, Paul
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Verhoog, Matthijs
bcd28eee-05b2-4a4d-980a-893d969b5530
Mansvelder, Huibert
fa35a895-4305-4709-90c5-62b155047ecf
Perry, V. Hugh
1cfaa2eb-cd6c-439e-9db3-b4258f3235e6
Bulters, Diederik
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Vargas-Caballero, Mariana, Pegasiou, Chrysia-Maria, Zolnourian, Ardalan, Gomez-Nicola, Diego, Deinhardt, Katrin, Nicoll, James, Ahmed, Aminul, Vajramani, Girish V., Grundy, Paul, Verhoog, Matthijs, Mansvelder, Huibert, Perry, V. Hugh and Bulters, Diederik
(2020)
Age dependent changes in synaptic NMDA receptor composition in adult human cortical neurons.
Cerebral Cortex, 30 (7), , [bhaa052].
(doi:10.1093/cercor/bhaa052).
Abstract
The molecular processes underlying the aging-related decline in cognitive performance and memory observed in humans are poorly understood. Studies in rodents have shown a decrease in N-methyl-D-aspartate receptors (NMDARs) that contain the GluN2B subunit in aging synapses, and this decrease is correlated with impaired memory functions. However, the age-dependent contribution of GluN2B-containing receptors to synaptic transmission in human cortical synapses has not been previously studied. We investigated the synaptic contribution of GluN2A and GluN2B-containing NMDARs in adult human neurons using fresh nonpathological temporal cortical tissue resected during neurosurgical procedures. The tissue we obtained fulfilled quality criteria by the absence of inflammation markers and proteomic degradation. We show an age-dependent decline in the NMDA/AMPA receptor ratio in adult human temporal cortical synapses. We demonstrate that GluN2B-containing NMDA receptors contribute to synaptic responses in the adult human brain with a reduced contribution in older individuals. With previous evidence demonstrating the critical role of synaptic GluN2B in regulating synaptic strength and memory storage in mice, this progressive reduction of GluN2B in the human brain during aging may underlie a molecular mechanism in the age-related decline in cognitive abilities and memory observed in humans.
Text
Age dependent changes in synaptic NMDA
- Accepted Manuscript
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Accepted/In Press date: 7 February 2020
e-pub ahead of print date: 17 March 2020
Published date: 7 July 2020
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© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Keywords:
NR2A, NR2B, human, resected, surgical
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Local EPrints ID: 438981
URI: http://eprints.soton.ac.uk/id/eprint/438981
ISSN: 1047-3211
PURE UUID: 456f2ba6-ff99-4b0e-ad7c-73ba5e599a03
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Date deposited: 31 Mar 2020 16:30
Last modified: 17 Mar 2024 05:26
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Author:
Chrysia-Maria Pegasiou
Author:
Ardalan Zolnourian
Author:
Aminul Ahmed
Author:
Girish V. Vajramani
Author:
Paul Grundy
Author:
Matthijs Verhoog
Author:
Huibert Mansvelder
Author:
V. Hugh Perry
Author:
Diederik Bulters
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