Cited by 87Stress Responses and CortisolNeuropeptides and Animal PhysiologyNeuroscience of respiration and sleep

Identification of chronic stress‐activated regions reveals a potential recruited circuit in rat brain

Open access
Flak, Jonathan N., Solomon, Matia B., Jankord, Ryan, Krause, Eric G., Herman, James P.·2012·European Journal of Neuroscience

Abstract

Chronic stress induces presynaptic and postsynaptic modifications in the paraventricular nucleus of the hypothalamus that are consistent with enhanced excitatory hypothalamo‐pituitary‐adrenocortical (HPA) axis drive. The brain regions mediating these molecular modifications are not known. We hypothesized that chronic variable stress (CVS) tonically activates stress‐excitatory regions that interact with the paraventricular nucleus of the hypothalamus, culminating in stress facilitation. In order to identify chronically activated brain regions, ΔFosB, a documented marker of tonic neuronal activation, was assessed in known stress regulatory limbic and brainstem sites. Four experimental groups were included: CVS, repeated restraint (RR) (control for HPA habituation), animals weight‐matched (WM) to CVS animals (control for changes in circulating metabolic factors due to reduced weight gain), and non‐handled controls. CVS, (but not RR or WM) induced adrenal hypertrophy, indicating that sustained HPA axis drive only occurred in the CVS group. CVS (but not RR or WM) selectively increased the number of FosB/ΔFosB nuclei in the nucleus of the solitary tract, posterior hypothalamic nucleus, and both the infralimbic and prelimbic divisions of the medial prefrontal cortex, indicating an involvement of these regions in chronic drive of the HPA axis. Increases in FosB/ΔFosB‐immunoreactive cells were observed following both RR and CVS in the other regions (e.g. the dorsomedial hypothalamus), suggesting activation by both habituating and non‐habituating stress conditions. The data suggest that unpredictable stress uniquely activates interconnected cortical, hypothalamic, and brainstem nuclei, potentially revealing the existence of a recruited circuitry mediating chronic drive of brain stress effector systems.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/j.1460-9568.2012.08161.x

Cites

80 of 80 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The infralimbic cortex is involved in coping with chronic stress, eventually leading to structural changes and prefrontal dysfunction.

    “The most ventral subdomain of the mPFC is the infralimbic cortex (IL) and is involved in coping with chronic stress eventually leading to structural changes and prefrontal dysfunction [5–11].”

    From Development of prefrontal cortex (2022) · cites this paper as [5]

    The Results (Upstream Limbic Structures) report increased FosB/ΔFosB expression in the infralimbic cortex after chronic variable stress. The Discussion suggests that prefrontal activation may produce lasting changes in gene transcription and contribute to dysfunction, but does not establish that infralimbic involvement in coping leads to structural changes or prefrontal dysfunction. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. McClave JTaD F H II Statistics 1994 Sixth Edition

Cited by

Sorted by citations

Authors
Flak, J. N., Solomon, M. B., Jankord, R., Krause, E. G., & Herman, J. P.
Affiliations
University of Cincinnati (US)
Corresponding author
Herman, James P.
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2012-07-12
Volume
36
Issue
4
Pages
2547-2555
ISSN
  • 0953-816X (ISSN-L)
  • 1460-9568
OpenAlex
W2102295712
Cited by
87
References
80
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 9 · 2018: 10 · 2017: 5 · 2016: 20 · 2015: 8 · 2014: 5 · 2013: 8
FWCI
2.79
Type
journal article
Language
en
Open access
Locations
  • European Journal of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (R01MH049698, MH069860, R01MH069860, MH049698)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords
chronic variable stress, chronic stress, ΔFosB, FosB, paraventricular nucleus, hypothalamic-pituitary-adrenal axis, nucleus tractus solitarius, posterior hypothalamic nucleus, infralimbic cortex, prelimbic cortex, medial prefrontal cortex, adrenal hypertrophy
MeSH terms
Animals, Brain Stem, Limbic System, Male, Stress, Psychological, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review