CoChat
Sign Up
Cited by 138Stress Responses and CortisolTreatment of Major DepressionTryptophan and brain disorders

Chronic unpredictable stress promotes neuronal apoptosis in the cerebral cortex

Open access
Bachis, Alessia, Cruz, Maria Idalia, Nosheny, Rachel L., Mocchetti, Italo·2008·Neuroscience Letters
DOI 10.1016/j.neulet.2008.06.081PMC PMC2543936
Open this paper in CoChat — free account

Abstract

Stress-mediated loss of synaptogenesis in the hippocampus appears to play a role in depressive and mood disorders. However, little is known about the effect of stress/depression on the plasticity and survival of cortical neurons. In this report, we have examined whether chronic stress increases the vulnerability of neurons in the rat cortex. We have used a chronic unpredictable mild stress (CMS) as a rat model of depression. CMS (5 weeks treatment) produced anedonia and increased corticosterone levels. These effects were accompanied by a detectable increase in caspase-3 positive neurons in the cerebral cortex, suggesting apoptosis. Desipramine (DMI), a well known antidepressant, reversed the pro-apoptotic effect of CMS. These results suggest that antidepressants may reduce the pathological changes seen in stress-induced depressive disorders.

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 · 10.1016/j.neulet.2008.06.081

Cites

4 of 4 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?

  • Cortical neuron atrophy and dysfunction is observed in rodents following chronic corticosterone administration, chronic unpredictable mild stress, chronic restraint stress, and chronic social defeat stress.

    “Cortical neuron atrophy and dysfunction is observed in rodents following chronic corticosterone administration (121), chronic unpredictable mild stress (122, 123), chronic restraint stress (48, 49, 124, 125), and chronic social defeat stress (126–128).”

    From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [123]

    The Abstract reports that five weeks of chronic unpredictable mild stress in rats increased caspase-3-positive neurons in the cerebral cortex, suggesting apoptosis. The conclusion proposes that cortical apoptosis may help explain loss of neuronal function, but the paper does not report cortical neuron atrophy or directly measure neuronal dysfunction. The other stress paradigms in the citing sentence are attached to different citations. (LLM, conf=0.86)

    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: 37

  1. [1]Ankarcrona M Dypbukt JM Bonfoco E Zhivotovsky B Orrenius S Lipton SA Nicotera P Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function Neuron 1995 15 961 973 7576644
  2. [2]Bachis A Aden SA Nosheny RL Andrews PM Mocchetti I Axonal transport of Human Immunodeficiency Virus Type 1 envelope glycoprotein 120 is found in association with neuronal apoptosis J. Neurosci 2006 26 6771 6780 16793884 PMC6673819
  3. [3]Bal-Klara A Bird MM The effects of various antidepressant drugs on the fine-structure of neurons of the cingulate cortex in culture Neuroscience 1990 37 685 692 2247218
  4. [4]Barnabe-Heider F Miller FD Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways J Neurosci 2003 23 5149 5160 12832539 PMC6741181
  5. [5]Bekris S Antoniou K Daskas S Papadopoulou-Daifoti Z Behavioural and neurochemical effects induced by chronic mild stress applied to two different rat strains Behav Brain Res 2005 161 45 59 15904709
  6. [6]Carrasco J Penkowa M Giralt M Camats J Molinero A Campbell IL Palmiter RD Hidalgo J Role of metallothionein-III following central nervous system damage Neurobiol Dis 2003 13 22 36 12758064
  7. [7]Czeh B Michaelis T Watanabe T Frahm J de Biurrun G van Kampen M Bartolomucci A Fuchs E Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine Proc Natl Acad Sci U S A 2001 98 12796 12801 11675510 PMC60133
  8. [8]Delgado PL How antidepressants help depression: mechanisms of action and clinical response J. Clin Psychiatry 2004 65 Suppl 4 25 30 15046538
  9. [9]DeVries AC Joh HD Bernard O Hattori K Hurn PD Traystman RJ Alkayed NJ Social stress exacerbates stroke outcome by suppressing Bcl-2 expression Proc Natl Acad Sci U S A 2001 98 11824 11828 11553785 PMC58815
  10. [10]Duman RS Role of neurotrophic factors in the etiology and treatment of mood disorders Neuromolecular Med 2004 5 11 25 15001809
  11. [11]Eastwood SL Harrison PJ Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins Brain Res Bull 2001 55 569 578 11576753
  12. [12]Ghosh A Carnahan J Greenberg ME Requirement for BDNF in activity-dependent survival of cortical neurons Science 1994 263 1618 1623 7907431
  13. [13]Gillespie CF Nemeroff CB Hypercortisolemia and Depression Psychosom Med 2005 67 S26 S28 15953796
  14. [15]Gould E Tanapat P Stress and hippocampal neurogenesis Biol Psychiatry 1999 46 1472 1479 10599477
  15. [16]Haack D Luu H Cho J Chen MJ Russo-Neustadt A Exercise reverses chronic stress-induced Bax oligomer formation in the cerebral cortex Neurosci Lett 2008 438 290 294 18487019 PMC2515610
  16. [17]Haynes LE Griffiths MR Hyde RE Barber DJ Mitchell IJ Dexamethasone induces limited apoptosis and extensive sublethal damage to specific subregions of the striatum and hippocampus: implications for mood disorders Neuroscience 2001 104 57 69 11311531
  17. [18]Korada S Zheng W Basilico C Schwartz ML Vaccarino FM Fibroblast growth factor 2 is necessary for the growth of glutamate projection neurons in the anterior neocortex J Neurosci 2002 22 863 875 11826116 PMC6758485
  18. [19]Lenze E Cross D McKeel D Neuman RJ Sheline YI White matter hyperintensities and gray matter lesions in physically healthy depressed subjects Am J Psychiatry 1999 156 1602 1607 10518173
  19. [20]Leonard BE Evidence for a biochemical lesion in depression J. Clin. Psychiatry 2000 61 Suppl 6 12 17 10775019
  20. [21]Leonard BE The HPA and immune axes in stress: The involvement of the serotonergic system Eur Psychiatry 2005 20 S302 S306 16459240
  21. [22]Li AJ Suzuki S Suzuki M Mizukoshi E Imamura T Fibroblast growth factor-2 increases functional excitatory synapses on hippocampal neurons Eur J Neurosci 2002 16 1313 1324 12405992
  22. [23]Lucassen PJ Heine VM Muller MB van der Beek EM Wiegant VM De Kloet ER Joels M Fuchs E Swaab DF Czeh B Stress, depression and hippocampal apoptosis CNS & neurological disorders drug targets 2006 5 531 546 17073656
  23. [24]Lucassen PJ Vollmann-Honsdorf GK Gleisberg M Czeh B De Kloet ER Fuchs E Chronic psychosocial stress differentially affects apoptosis in hippocampal subregions and cortex of the adult tree shrew Eur J Neurosci 2001 14 161 166 11488960
  24. [25]Malberg JE Eisch AJ Nestler EJ Duman RS Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus J Neurosci 2000 20 9104 9110 11124987 PMC6773038
  25. [26]Mallei A Shi B Mocchetti I Antidepressant treatments induce the expression of basic fibroblast growth factor in cortical and hippocampal neurons Mol Pharmacol 2002 61 1017 1024 11961119
  26. [28]Merali Z Brennan K Brau P Anisman H Dissociating anorexia and anhedonia elicited by interleukin-1beta: antidepressant and gender effects on responding for "free chow" and "earned" sucrose intake Psychopharmacology (Berl) 2003 165 413 418 12459927
  27. [29]Monleon S D'Aquila P Parra A Simon VM Brain PF Willner P Attenuation of sucrose consumption in mice by chronic mild stress and its restoration by imipramine Psychopharmacology (Berl) 1995 117 453 457 7604147
  28. [30]Moreau JL Borgulya J Jenck F Martin JR Tolcapone: a potential new antidepressant detected in a novel animal model of depression Behav Pharmacol 1994 5 344 350 11224284
  29. [32]Nolan CL Moore GJ Madden R Farchione T Bartoi M Lorch E Stewart CM Rosenberg DR Prefrontal cortical volume in childhood-onset major depression: preliminary findings Arch Gen Psychiatry 2002 59 173 179 11825139
  30. [33]Nosheny RL Bachis A Acquas E Mocchetti I Human immunodeficiency virus type 1 glycoprotein gp120 reduces the levels of brain-derived neurotrophic factor in vivo: potential implication for neuronal cell death Eur J Neurosci 2004 20 2857 2864 15579139
  31. [35]Perera TD Coplan JD Lisanby SH Lipira CM Arif M Carpio C Spitzer G Santarelli L Scharf B Hen R Rosoklija G Sackeim HA Dwork AJ Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates J. Neurosci 2007 27 4894 4901 17475797 PMC6672102
  32. [36]Petrie RX Reid IC Stewart CA The N-methyl-D-aspartate receptor, synaptic plasticity, and depressive disorder. A critical review Pharmacol Ther 2000 87 11 25 10924739
  33. [37]Sanchez C Gruca P Papp M R-citalopram counteracts the antidepressant-like effect of escitalopram in a rat chronic mild stress model Behav Pharmacol 2003 14 465 470 14501259
  34. [38]Santarelli L Saxe M Gross C Surget A Battaglia F Dulawa S Weisstaub N Lee J Duman R Arancio O Belzung C Hen R Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants Science 2003 301 805 809 12907793
  35. [39]Sheline YI Gado MH Kraemer HC Untreated depression and hippocampal volume loss Am J Psychiatry 2003 160 1516 1518 12900317
  36. [40]Willner P Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation Psychopharmacology (Berl) 1997 134 319 329 9452163
  37. [41]Yuan J Yankner BA Apoptosis in the nervous system Nature 2000 407 802 809 11048732

Cited by

Sorted by citations

Authors
Bachis, A., Cruz, M. I., Nosheny, R. L., & Mocchetti, I.
Affiliations
Georgetown University Medical Center (US)
Corresponding author
Mocchetti, Italo
ORCID
Venue
Neuroscience Letters
Publisher
Elsevier BV
Published
2008-09
Volume
442
Issue
2
Pages
104-108
ISSN
0304-3940 (ISSN-L)
DOI
10.1016/j.neulet.2008.06.081
PMC
PMC2543936
OpenAlex
W1989239600
Cited by
138
References
4
Citations by year
2026: 5 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 14 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 8 · 2012: 14
FWCI
3.92
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience Letters (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (R21MH071848)
  • National Institute of Neurological Disorders and Stroke (NS047977, R21NS047977)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
chronic unpredictable mild stress, neuronal apoptosis, cerebral cortex, depression, caspase-3, corticosterone, desipramine, antidepressants, neuronal survival, rat model of depression
MeSH terms
Animals, Antidepressive Agents, Tricyclic, Cerebral Cortex, Chronic Disease, Corticosterone, Desipramine, Disease Models, Animal, Male, Neurons, Stress, Psychological, Rats, Sprague-Dawley, Apoptosis, Rats, Caspase 3

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