Evidence for reduced experience-dependent dendritic spine plasticity in the aging prefrontal cortex
Open accessAbstract
Cognitive functions that require the prefrontal cortex are highly sensitive to aging in humans, nonhuman primates, and rodents, although the neurobiological correlates of this vulnerability remain largely unknown. It has been proposed that dendritic spines represent the primary site of structural plasticity in the adult brain, and recent data have supported the hypothesis that aging is associated with alterations of dendritic spine morphology and plasticity in prefrontal cortex. However, no study to date has directly examined whether aging alters the capacity for experience-dependent spine plasticity in aging prefrontal neurons. To address this possibility, we used young, middle-aged, and aged rats in a behavioral stress paradigm known to produce spine remodeling in prefrontal cortical neurons. In young rats, stress resulted in dendritic spine loss and altered patterns of spine morphology; in contrast, spines from middle-aged and aged animals were remarkably stable and did not show evidence of remodeling. The loss of stress-induced spine plasticity observed in aging rats occurred alongside robust age-related reductions in spine density and shifts in remaining spine morphology. Together, the data presented here provide the first evidence that experience-dependent spine plasticity is altered by aging in prefrontal cortex, and support a model in which dendritic spines become progressively less plastic in the aging brain.
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Dendritic spines appear to lose their resilience in very old brains.
“As dendritic spines appear to lose their resilience in very old brains (Bloss et al., 2011)”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Bloss et al., 2011
The Results section reports age-related loss of thin and stubby spines and reduced experience-dependent spine plasticity, supporting an age-related change in some spines. But the study examines rat prefrontal cortex, not very old brains generally; its Discussion also says mushroom spines remain mostly resistant to aging. No page numbers were available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn young adult rodents, layer II/III PFC pyramidal cell dendrites can regrow with sufficient time spent under safe conditions, but this plasticity is lost with advanced age.
“In young adult rodents, layer II/III PFC pyramidal cell dendrites can regrow with sufficient time spent under safe conditions, but this plasticity is lost with advanced age76.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [76]
The Results section, “Stress and dendritic spine plasticity in young animals,” reports modest spine regrowth after a three-week recovery period; the Discussion reports that stress-related spine changes were absent in aged rats. The claim goes further by saying that dendrites themselves regrow in young animals but lose that regrowth capacity with age. This study directly tested spine plasticity, not age-related loss of dendritic regrowth. (LLM, conf=0.87)
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- Authors
- Bloss, E. B., Janssen, W. G., Ohm, D. T., Yuk, F. J., Wadsworth, S., Saardi, K. M., McEwen, B. S., & Morrison, J. H.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Rockefeller University (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-05-25
- Volume
- 31
- Issue
- 21
- Pages
- 7831-7839
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3398699
- OpenAlex
- W2065400194
- Cited by
- 219
- References
- 56
- Citations by year
- 2026: 16 · 2025: 8 · 2024: 8 · 2023: 19 · 2022: 13 · 2021: 10 · 2020: 12 · 2019: 13 · 2018: 18 · 2017: 10 · 2016: 18 · 2015: 17 · 2014: 14 · 2013: 18 · 2012: 21
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R37AG006647, F31AG034794)
- National Institute of Mental Health (MH-58911, P50MH058911)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- dendritic spine plasticity, aging, prefrontal cortex, experience-dependent plasticity, dendritic spine density, dendritic spine morphology, cognitive aging
- MeSH terms
- Aging, Animals, Cognition, Learning, Male, Neuronal Plasticity, Rats, Sprague-Dawley, Prefrontal Cortex, Dendritic Spines, Rats
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