Mechanisms of late-onset cognitive decline after early-life stress
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Progressive cognitive deficits that emerge with aging are a result of complex interactions of genetic and environmental factors. Whereas much has been learned about the genetic underpinnings of these disorders, the nature of "acquired" contributing factors, and the mechanisms by which they promote progressive learning and memory dysfunction, remain largely unknown. Here, we demonstrate that a period of early-life "psychological" stress causes late-onset, selective deterioration of both complex behavior and synaptic plasticity: two forms of memory involving the hippocampus, were severely but selectively impaired in middle-aged, but not young adult, rats exposed to fragmented maternal care during the early postnatal period. At the cellular level, disturbances to hippocampal long-term potentiation paralleled the behavioral changes and were accompanied by dendritic atrophy and mossy fiber expansion. These findings constitute the first evidence that a short period of stress early in life can lead to delayed, progressive impairments of synaptic and behavioral measures of hippocampal function, with potential implications to the basis of age-related cognitive disorders in humans.
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Early life stress produces a delayed effect that reduces cognitive function and the number of CA3 neurons as well as decreased branching of hippocampal pyramidal neurons.
“early life stress produces a delayed effect that reduces cognitive function and the number of CA3 neurons as well as decreased branching of hippocampal pyramidal neurons (Brunson et al., 2001; Brunson et al., 2005).”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Brunson et al., 2005
CRF in the hippocampus is expressed in a subset of GABA neurons (Cajal-Retzius cells) in the developing hippocampus.
“CRF in the hippocampus is expressed in a subset of GABA neurons (Cajal-Retzius cells) in the developing hippocampus”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Brunson et al., 2005
Early life stress produces a delayed effect that reduces cognitive function and the number of CA3 neurons, as well as decreased branching of hippocampal pyramidal neurons.
“CRF in the hippocampus is expressed in a subset of GABA neurons (Cajal-Retzius cells) in the developing hippocampus, and early life stress produces a delayed effect that reduces cognitive function and the number of CA3 neurons, as well as decreased branching of hippocampal pyramidal neurons.86,87”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [87]
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- Authors
- Brunson, K. L., Kramár, E., Lin, B., Chen, Y., Colgin, L. L., Yanagihara, T. K., Lynch, G., & Baram, T. Z.
- Affiliations
- University of California, Irvine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-10-12
- Volume
- 25
- Issue
- 41
- Pages
- 9328-9338
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3100717
- OpenAlex
- W1988059569
- Cited by
- 479
- References
- 76
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 28 · 2023: 24 · 2022: 30 · 2021: 37 · 2020: 31 · 2019: 26 · 2018: 25 · 2017: 20 · 2016: 26 · 2015: 21 · 2014: 27 · 2013: 26 · 2012: 18
- FWCI
- 6.26
- 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)
- eScholarship (California Digital Library) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- National Institutes of Health (T32 AG00096, NS045260, AG00096)
- National Institute on Aging (T32 AG00096, T32AG000096)
- National Institute of Neurological Disorders and Stroke (P01NS045260, NS 28912, NS045260, R01NS028912, NS 39307, R01NS039307)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- early life stress, hippocampus, synaptic plasticity, long-term potentiation, dendritic atrophy, age-related cognitive decline, learning and memory impairment, postpartum stress, rats
- MeSH terms
- Age Factors, Animals, Cognition Disorders, Female, Hippocampus, Male, Maternal Behavior, Stress, Psychological, Time Factors, Rats, Sprague-Dawley, Age of Onset, Long-Term Potentiation, Rats, In Vitro Techniques
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