Age-related alterations to working memory and to pyramidal neurons in the prefrontal cortex of rhesus monkeys begin in early middle-age and are partially ameliorated by dietary curcumin.
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Layer 3 (L3) pyramidal neurons in aged rhesus monkey lateral prefrontal cortex (LPFC) exhibit significantly elevated excitability in vitro and reduced spine density compared to neurons in young subjects. The time-course of these alterations, and whether they can be ameliorated in middle age by the powerful anti-oxidant curcumin is unknown. We compared the properties of L3 pyramidal neurons from the LPFC of behaviorally characterized rhesus monkeys over the adult lifespan using whole-cell patch clamp recordings and neuronal reconstructions. Working memory (WM) impairment, neuronal hyperexcitability, and spine loss began in middle age. There was no significant relationship between neuronal properties and WM performance. Middle-aged subjects given curcumin exhibited better WM performance and less neuronal excitability compared to control subjects. These findings suggest that the appropriate time frame for intervention for age-related cognitive changes is early middle age, and points to the efficacy of curcumin in delaying WM decline. Because there was no relationship between excitability and behavior, the effects of curcumin on these measures appear to be independent.
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Aging itself aberrantly impacts the medial prefrontal cortex at a localized pyramidal neuronal level, with such neurodegenerative changes perhaps beginning as early as middle age.
“Therefore suggesting aging itself aberrantly impacts the mPFC at a localized pyramidal neuronal level, with such neurodegenerative changes perhaps beginning as early as middle age, as was found from patch clamp recordings in non‐human primates. 68”
From High vulnerability of medial prefrontal pyramidal neurons in post-stroke, vascular, Alzheimer's disease, and aging-related dementias (2026) · cites this paper as [68]
The Discussion reports that age-related physiological changes in layer 3 pyramidal neurons were evident by middle age, and the Methods confirm that the study used whole-cell patch-clamp recordings in rhesus monkeys (page numbers unavailable). But the neurons studied were in the lateral prefrontal cortex (LPFC), not the medial prefrontal cortex (mPFC); the paper describes physiological and structural alterations rather than establishing neurodegeneration. (LLM, conf=0.90)
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References 86 · Cited by 20
- Authors
- Chang, W., Weaver, C., Medalla, M., Moore, T., & Luebke, J.
- Affiliations
- Boston University (US)
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 109
- Pages
- 113-124
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC8671373
- OpenAlex
- W3200871977
- Cited by
- 20
- References
- 86
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 8
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH
- National Institute on Aging (R01-AG043478, R01-AG043640, R01-AG059028)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- working memory, age-related cognitive decline, rhesus monkeys, prefrontal cortex, neuronal excitability, dendritic spine density, curcumin, dietary intervention, middle age (human life stage), antioxidants
- MeSH terms
- Age Factors, Aging, Animals, Curcumin, Female, Macaca mulatta, Male, Memory, Short-Term, Time Factors, Prefrontal Cortex, Pyramidal Cells, Patch-Clamp Techniques, Dietary Supplements
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