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Synapses are lost during aging in the primate prefrontal cortex
Open accessAbstract
An electron microscopic analysis has been carried out on the effects of age on the numerical density of both excitatory (asymmetric) and inhibitory (symmetric) synapses in the neuropil of layers 2/3 and of layer 5 in area 46 from the frontal cortex of behaviorally tested rhesus monkeys. There is no change in the lengths of synaptic junctions with age or in the percentage distribution of synapses relative to the postsynaptic spines and dendritic shafts. However, in layers 2/3 there is an overall loss of about 30% of synapses from 5 to 30 years of age, and both asymmetric and symmetric synapses are lost at the same rate. In layer 5 the situation is different; the overall loss of synapses is only 20% and this is almost entirely due to a loss of asymmetric synapses, since there is no significant loss of symmetric synapses from this layer with age. When the synapse data are correlated with the overall cognitive impairment shown by the monkeys, it is found that there is a strong correlation between the numerical density of asymmetric synapses in layers 2/3 and cognitive impairment, with a weaker correlation between symmetric synapse loss and cognitive impairment. In layer 5 on the other hand there is no correlation between synapse loss and cognitive impairment. However synapse loss is not the only factor causing cognitive impairment, since in previous studies of area 46 we have found that age-related alteration in myelin in this frontal area also significantly contributes to cognitive decline. The synapse loss is also considered in light of earlier studies, which show that the frequency of spontaneous excitatory synaptic responses is reduced with age in layers 2/3 neurons.
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“In fact, quantitative analyses of synapses in the neuropil have shown that most synapses on dendritic shafts are AS (∼80%), with relatively few being SS (∼20%) (Beaulieu et al., 1992; Peters et al., 2008; Hsu et al., 2017; Calì et al., 2018; Santuy et al., 2018b; Domínguez-Álvaro et al., 2019, 2021a,b; Yakoubi et al., 2019b; Montero-Crespo et al., 2020, 2021; Cano-Astorga et al., 2021, 2023;”
From Unambiguous identification of asymmetric and symmetric synapses using volume electron microscopy (2024) · cites this paper as Peters et al., 2008
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Metadata
- Authors
- Peters, A., Sethares, C., & Luebke, J. I.
- Affiliations
- Boston University (US)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 152
- Issue
- 4
- Pages
- 970-981
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2441531
- OpenAlex
- W2021005581
- Cited by
- 268
- References
- 50
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 16 · 2023: 23 · 2022: 10 · 2021: 20 · 2020: 14 · 2019: 13 · 2018: 17 · 2017: 11 · 2016: 17 · 2015: 8 · 2014: 13 · 2013: 22 · 2012: 21
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG025062, P01AG000001, P01-AG-00001)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- synaptic loss, aging, prefrontal cortex, rhesus monkeys, area 46, asymmetric synapses, symmetric synapses, cognitive impairment, layer 2/3, layer 5, myelin, postsynaptic spines
- MeSH terms
- Age Factors, Aging, Animals, Behavior, Animal, Female, Macaca mulatta, Male, Neurons, Synapses, Prefrontal Cortex, Microscopy, Electron, Transmission
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