Cited by 100Stress Responses and CortisolNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats

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Lin, Y., Ter Horst, G. J., Wichmann, R., Bakker, P., Liu, A., Li, X., Westenbroek, C.·2009·Cerebral Cortex

Abstract

Studies show that sex plays a role in stress-related depression, with women experiencing a higher vulnerability to its effect. Two major targets of antidepressants are brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element-binding protein (CREB). The aim of this study was to investigate the levels of CREB, phosphorylation of CREB (pCREB), and BDNF in stress-related brain regions of male and female rats after stress and recovery. CREB and pCREB levels were examined in CA1, CA2, CA3, paraventricular nucleus of the thalamus (PVT), amygdala, anterior cingulate area, dorsal part (ACAd), and infralimbic area of prefrontal cortex (PFC), whereas dentate gyrus (DG) and prelimbic area (PL) of PFC were examined for BDNF levels. Our results demonstrate that levels of CREB and pCREB in male CA1, CA2 and CA3, PVT, amygdala, and ACAd were reduced by stress, whereas the same brain regions of female rats exhibited no change. BDNF levels were decreased by chronic stress in female PL but were increased by acute stress in female DG. BDNF levels in male DG and PL were found not to undergo change in response to stress. Abnormalities in morphology occurred after chronic stress in males but not in females. In all cases, the levels of CREB, pCREB, and BDNF in recovery animals were comparable to the levels of these proteins in control animals. These findings demonstrate a sexual dimorphism in the molecular response to stress and suggest that these differences may have important implications for potential therapeutic treatment of depression.

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  • Chronic glucocorticoid exposure reduces brain-derived neurotrophic factor levels in the PFC, as does chronic stress, but it is not yet known whether this contributes to the observed dendritic changes.

    “Chronic glucocorticoid exposure also reduces brain-derived neurotrophic factor levels in the PFC119, as does chronic stress120, but it is not yet known whether this contributes to the observed dendritic changes.”

    From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [120]

    Citation 120 attaches to the chronic-stress portion of the sentence, not the glucocorticoid-exposure claim. The Results section (“BDNF Levels in Male and Female PL and DG”; page not available in our copy) reports reduced BDNF in the prelimbic PFC after chronic stress in female rats, but no significant change in male rats. The unqualified claim omits that sex-specific limit. (LLM, conf=0.90)

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Research works printed but not linked: 1

  1. Conkright MD Canettieri G Screaton R Guzman E Miraglia L Hogenesch JB Montminy M TORCs: transducers of regulated CREB activity Mol Cell 2003 12 413 423 14536081

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Authors
Lin, Y., Ter Horst, G. J., Wichmann, R., Bakker, P., Liu, A., Li, X., & Westenbroek, C.
Affiliations
  • University Medical Center Groningen (NL)
  • Peking University (CN)
Venue
Cerebral Cortex
Published
2008-12-10
Volume
19
Issue
9
Pages
1978-1989
ISSN
  • 1047-3211 (ISSN-L)
  • 1460-2199
OpenAlex
W2145152438
Cited by
100
References
86
Citations by year
2026: 1 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 6 · 2013: 7 · 2012: 10
FWCI
2.71
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Cerebral Cortex (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders
  • Rijksuniversiteit Groningen
  • Universitair Medisch Centrum Groningen
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
sex differences, chronic stress, acute stress, stress recovery, depression, CREB, CREB phosphorylation, brain-derived neurotrophic factor, hippocampus, paraventricular thalamus, amygdala, anterior cingulate cortex, prefrontal cortex, dentate gyrus, prelimbic cortex, sexual dimorphism, antidepressant targets
MeSH terms
Acute Disease, Animals, Brain, Female, Male, Neuronal Plasticity, Sex Factors, Stress, Psychological, Tissue Distribution, Rats, Wistar, Cyclic AMP Response Element-Binding Protein, Brain-Derived Neurotrophic Factor, Recovery of Function, CREB-Binding Protein, Rats

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