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Chronic stress alters synaptic terminal structure in hippocampus

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Magariños, Ana María, Verdugo, José M. García, McEwen, Bruce S.·1997·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.94.25.14002PMC PMC28422
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Abstract

Repeated psychosocial or restraint stress causes atrophy of apical dendrites in CA3 pyramidal neurons of the hippocampus, accompanied by specific cognitive deficits in spatial learning and memory. Excitatory amino acids mediate this atrophy together with adrenal steroids and the neurotransmitter serotonin. Because the mossy fibers from dentate granule neurons provide a major excitatory input to the CA3 proximal apical dendrites, we measured ultrastructural parameters associated with the mossy fiber–CA3 synapses in control and 21-day restraint-stressed rats in an effort to find additional morphological consequences of stress that could help elucidate the underlying anatomical as well as cellular and molecular mechanisms. Although mossy fiber terminals of control rats were packed with small, clear synaptic vesicles, terminals from stressed animals showed a marked rearrangement of vesicles, with more densely packed clusters localized in the vicinity of active zones. Moreover, compared with controls, restraint stress increased the area of the mossy fiber terminal occupied by mitochondrial profiles and consequently, a larger, localized energy-generating capacity. A single stress session did not produce these changes either immediately after or the next day following the restraint session. These findings provide a morphological marker of the effects of chronic stress on the hippocampus that points to possible underlying neuroanatomical as well as cellular and molecular mechanisms for the ability of repeated stress to cause structural changes within the hippocampus.

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  • Stress results in atrophy of the hippocampus and medial PFC (mPFC).

    “By contrast, stress results in atrophy of the hippocampus and medial PFC (mPFC) (Magariños et al., 1997, Vyas et al., 2002, Radley et al., 2006).”

    From The impact of developmental timing for stress and recovery (2015) · cites this paper as Magariños et al., 1997

  • Chronic restraint stress increases the release of glutamate.

    “Taken together with the fact that vesicles that remain in the mossy fiber terminal are near active synaptic zones and that there are more mitochondria in the terminals of stressed rats, this suggests that chronic restraint stress increases the release of glutamate (Magarinos et al., 1997).”

    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 Magarinos et al., 1997

  • 21-day chronic restraint stress leads to depletion of clear vesicles from mossy fiber terminals and increased expression of presynaptic proteins involved in vesicle release.

    “Moreover, 21d chronic restraint stress (CRS) leads to depletion of clear vesicles from mossy fiber terminals and increased expression of presynaptic proteins involved in vesicle release.73-75”

    From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [73]

  • Chronic restraint stress increases the release of glutamate.

    “Taken together with the fact that vesicles that remain in the mossy fiber terminal are near active synaptic zones and that there are more mitochondria in the terminals of stressed rats, this suggests that CRS increases the release of glutamate.73”

    From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [73]

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Authors
Magariños, A. M., Verdugo, J. M. G., & McEwen, B. S.
Affiliations
  • The Rockefeller University, 1230 York Avenue, New York, NY 10021; and University of Valencia, Burjassot, Valencia 46100, Spain
  • Universitat de València (ES)
ORCID
McEwen, Bruce S.
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1997-12-09
Volume
94
Issue
25
Pages
14002-14008
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.94.25.14002
PMC
PMC28422
OpenAlex
W2152541584
Cited by
543
References
3
Citations by year
2026: 10 · 2025: 9 · 2024: 12 · 2023: 8 · 2022: 16 · 2021: 14 · 2020: 19 · 2019: 10 · 2018: 21 · 2017: 13 · 2016: 19 · 2015: 26 · 2014: 20 · 2013: 27 · 2012: 25
FWCI
7.04
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Servier
  • National Institutes of Health (MH41256)
  • National Institute of Mental Health (MH-41256, R37MH041256, R01MH041256)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
chronic stress, restraint stress, hippocampus, mossy fiber-CA3 synapses, synaptic vesicles, active zone, mitochondria, CA3 pyramidal cells, dendritic atrophy, spatial learning and memory deficits, excitatory amino acids, adrenal steroids, serotonin, neuroplasticity
MeSH terms
Animals, Atrophy, Chronic Disease, Electrophysiology, Hippocampus, Male, Microscopy, Electron, Models, Neurological, Restraint, Physical, Seizures, Stress, Physiological, Stress, Psychological, Synapsins, Rats, Sprague-Dawley, Presynaptic Terminals, Rats

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