PT  - JOURNAL ARTICLE
AU  - C.M. Pegasiou
AU  - A. Zolnourian
AU  - D. Gomez-Nicola
AU  - K. Deinhardt
AU  - J.A.R. Nicoll
AU  - A.I. Ahmed
AU  - G. Vajramani
AU  - P. Grundy
AU  - M.B. Verhoog
AU  - H.D. Mansvelder
AU  - V.H. Perry
AU  - D. Bulters
AU  - M. Vargas-Caballero
TI  - Age dependent changes in synaptic NMDA receptor composition in adult human cortical neurons
AID  - 10.1101/2020.01.21.913475
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.21.913475
4099  - http://biorxiv.org/content/early/2020/02/12/2020.01.21.913475.short
4100  - http://biorxiv.org/content/early/2020/02/12/2020.01.21.913475.full
AB  - The molecular processes underlying the ageing-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 ageing 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 non-pathological 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 ageing may underlie a molecular mechanism in the age-related decline in cognitive abilities and memory observed in humans.