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Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex
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The hippocampus provided the gateway into much of what we have learned about stress and brain structural and functional plasticity, and this initial focus has expanded to other interconnected brain regions, such as the amygdala and prefrontal cortex. Starting with the discovery of adrenal steroid, and later, estrogen receptors in the hippocampal formation, and subsequent discovery of dendritic and spine synapse remodeling and neurogenesis in the dentate gyrus, mechanistic studies have revealed both genomic and rapid non-genomic actions of circulating steroid hormones in the brain. Many of these actions occur epigenetically and result in ever-changing patterns of gene expression, in which there are important sex differences that need further exploration. Moreover, glucocorticoid and estrogen actions occur synergistically with an increasing number of cellular mediators that help determine the qualitative nature of the response. The hippocampus has also been a gateway to understanding lasting epigenetic effects of early-life experiences. These findings in animal models have resulted in translation to the human brain and have helped change thinking about the nature of brain malfunction in psychiatric disorders and during aging, as well as the mechanisms of the effects of early-life adversity on the brain and the body.
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“Chronically elevated glucocorticoid levels, in turn, are known to induce remodeling of the hippocampus, amygdala, and mPFC [71]”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [71]
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“It has been proved that the changes in the structure and function of neurons may occur under the chronic stress and lead to the occurrence of MDD. 37 , 38”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [37]
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“These findings reveal alterations at the levels of intracellular signaling, gene expression, neurotrophic factors, neurogenesis, neuroinflammation, excitatory and inhibitory neurotransmission, and synaptic number and function, and have been described in several brain regions implicated in depression 13-22 .”
From Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model (2020) · cites this paper as [18]
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“Exaggerated fear is a core symptom of clinical anxiety and fear responding is closely linked to stress (Maren and Holmes, 2016;McEwen et al., 2016;Raio and Phelps, 2015), which (as described in Sections VI.G. and VII.H.) is tightly intertwined with gut-brain axis function.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as McEwen et al., 2016
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“Accompanying these behavioral changes are marked physiological and structural alterations, not only in the amygdala and hippocampus but, importantly, the PFC [98,99], that are similar to those seen in MDD.”
From Prefrontal cortex and depression (2022) · cites this paper as [99]
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“In rodents, the most abundant and consistent changes are in the mPFC (anterior cingulate, prelimbic and infralimbic) with somewhat more variable, mixed direction effects in the OFC (Fig. 3, top left-hand panel).”
From Prefrontal cortex and depression (2022) · cites this paper as [99]
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“Studies of chronic stress or glucocorticoid exposure in adult animals show notable effects on frontolimbic circuitry including dendritic atrophy of the mPFC and hippocampus, and expansion of the basolateral amygdala [71].”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [71]
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“In recent years, it has become increasingly clear that the effect of stress on neuronal morphology and functions varies across brain regions (53–56).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [56]
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Metadata
- Authors
- McEwen, B. S., Nasca, C., & Gray, J. D.
- Affiliations
- Rockefeller University (US)
- Venue
- Neuropsychopharmacology
- Published
- 2015-06-16
- Volume
- 41
- Issue
- 1
- Pages
- 3-23
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4677120
- OpenAlex
- W756325778
- Cited by
- 1,574
- References
- 218
- Citations by year
- 2026: 185 · 2025: 223 · 2024: 172 · 2023: 158 · 2022: 165 · 2021: 181 · 2020: 152 · 2019: 126 · 2018: 104 · 2017: 61 · 2016: 40 · 2015: 6
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Foundation for Suicide Prevention
- Hope for Depression Research Foundation
- National Institutes of Health (MH41256)
- National Institute of Mental Health (R01 MH41256, F32MH102065, R01MH041256)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- stress, hippocampus, amygdala, prefrontal cortex, neuroplasticity, dendritic remodeling, synaptic remodeling, dentate gyrus neurogenesis, glucocorticoids, estrogen receptor, non-genomic steroid action, epigenetics, sex differences, childhood adversity, early life experience, mental illness, brain aging
- MeSH terms
- Amygdala, Animals, Hippocampus, Humans, Nerve Net, Neuronal Plasticity, Neurons, Stress, Psychological, Prefrontal Cortex
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