Chronic Mild Stress Increases the Expression of Genes Encoding Proinflammatory Cytokines in the Rat Brain
Abstract
Alterations in the expression of genes encoding interleukins IL-1α, IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were studied in the rat brain in a model of a depressive disorder. We found that the signs of a depressionlike condition in rats, subjected to eight weeks of chronic mild unpredictable stress, were accompanied by increased IL-1α and IL-1β mRNAs levels in the neocortex, hippocampus, and brainstem and a decreased IL-6 mRNA level in the brainstem as compared to those observed in the control animals. We did not find any changes in the level of TNF-α mRNA. We suggest that region-specific alterations in the expression of cytokine genes, specifically, the most prominent increase in IL-1β expression, reflects greater vulnerability of chronically stressed animals to neuroinflammatory processes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Increased levels of pro-inflammatory cytokines have been reported in brain regions of stressed animals.
“and in brain regions of stressed animals [141,142,143].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [142]
Cites
1 retracted
Ma, C., Lingdong, K., Hongyan, L., & Ma, Z. (2016) · IUBMB Life · doi:10.1002/iub.1570 · Cited by 2 · see citing works
RetractedAnalysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369 · see citing works
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729 · see citing works
Depression: a new animal model sensitive to antidepressant treatments
PORSOLT, R. D., LE PICHON, M., & JALFRE, M. (1977) · Nature · doi:10.1038/266730a0 · Cited by 4,451 · see citing works
Willner, P., Towell, A., Sampson, D., Sophokleous, S., & Muscat, R. (1987) · Psychopharmacology · doi:10.1007/bf00187257 · Cited by 1,993 · see citing works
Willner, P. (1997) · Psychopharmacology · doi:10.1007/s002130050456 · Cited by 1,832 · see citing works
Willner, P. (2005) · Neuropsychobiology · doi:10.1159/000087097 · Cited by 1,605 · see citing works
Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor
Sapolsky, R., Rivier, C., Yamamoto, G., Plotsky, P., & Vale, W. (1987) · Science · doi:10.1126/science.2821621 · Cited by 1,504 · see citing works
State of the art review: depression, stress, anxiety, and cardiovascular disease
Cohen, B. E., Edmondson, D., & Kronish, I. M. (2015) · American Journal of Hypertension · doi:10.1093/ajh/hpv047 · Cited by 955 · see citing works
Cytokine, Sickness Behavior, and Depression
Dantzer, R. (2009) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2009.02.002 · Cited by 789 · see citing works
Cytokines and the Brain: Implications for Clinical Psychiatry
Kronfol, Z., & Remick, D. G. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.5.683 · Cited by 784 · see citing works
Assessing anhedonia in depression: potentials and pitfalls
Rizvi, S. J., Pizzagalli, D. A., Sproule, B. A., & Kennedy, S. H. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.004 · Cited by 571 · see citing works
Shelton, R. C., Claiborne, J., Sidoryk-Wegrzynowicz, M., Reddy, R., Aschner, M., Lewis, D. A., & Mirnics, K. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.52 · Cited by 511 · see citing works
Kubera, M., Obuchowicz, E., Goehler, L., Brzeszcz, J., & Maes, M. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.08.026 · Cited by 443 · see citing works
Cytokine–serotonin interaction through IDO: a neurodegeneration hypothesis of depression
Myint, A.-M., & Kim, Y. K. (2003) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00207-x · Cited by 376 · see citing works
Animal models of major depression and their clinical implications
Czéh, B., Fuchs, E., Wiborg, O., & Simon, M. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.04.004 · Cited by 375 · cited 1× · see citing works
“It is considered that chronic stress induced by various significant influences, first of all psychoemotional, results in the development of anxiety-depressive disorders (Cohen et al., 2015; Czeh et al., 2016).”
Coping with the Forced Swim Stressor: Towards Understanding an Adaptive Mechanism
de Kloet, E. R., & Molendijk, M. L. (2016) · Neural Plasticity · doi:10.1155/2016/6503162 · Cited by 353 · see citing works
Role of interleukin-1 beta in impairment of contextual fear conditioning caused by social isolation
Pugh, C. (1999) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00098-4 · Cited by 244 · see citing works
Bufalino, C., Hepgul, N., Aguglia, E., & Pariante, C. M. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.04.009 · Cited by 228 · see citing works
Farooq, R. K., Isingrini, E., Tanti, A., Guisquet, A. L., Arlicot, N., Minier, F., Leman, S., Chalon, S., Belzung, C., & Camus, V. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.03.020 · Cited by 177 · see citing works
Learned immobility explains the behavior of rats in the forced swimming test
Pablo, J. M. D., Parra, A., Segovia, S., & Guillamón, A. (1989) · Physiology & Behavior · doi:10.1016/0031-9384(89)90261-8 · Cited by 172 · see citing works
Rodent Models of Depression: Neurotrophic and Neuroinflammatory Biomarkers
Stepanichev, M. Y., Дыгало, Н. Н., Grigoryan, G. A., Shishkina, G. T., & Gulyaeva, N. V. (2014) · BioMed Research International · doi:10.1155/2014/932757 · Cited by 172 · see citing works
Catena-Dell’Osso, M., Bellantuono, C., Consoli, G., Baroni, S., Rotella, F., & Marazziti, D. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711794088353 · Cited by 149 · see citing works
Blandino, P., Barnum, C. J., Solomon, L. G., Larish, Y., Lankow, B. S., & Deak, T. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.04.013 · Cited by 137 · see citing works
Tao, W., Dong, Y. J., Su, Q., Wang, H., Chen, Y., Xue, W., Chen, C., Xia, B., Duan, J., & Chen, G. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.04.039 · Cited by 120 · see citing works
Models of Affective Illness: Chronic Mild Stress in the Rat
Papp, M. (2012) · Current Protocols in Pharmacology · doi:10.1002/0471141755.ph0509s57 · Cited by 61 · see citing works
Stepanichev, M. Y., Zdobnova, I. M., Yakovlev, A. A., Onufriev, M. V., Лазарева, Н. А., Zarubenko, I. I., & Gulyaeva, N. V. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10469 · Cited by 54 · see citing works
Rat strain differences in restraint stress-induced brain cytokines
Porterfield, V. M., Zimomra, Z. R., Caldwell, E. A., Camp, R. M., Gabella, K. M., & Johnson, J. D. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.05.023 · Cited by 53 · see citing works
Loftis, J. M., Patterson, A. L., Wilhelm, C., McNett, H., Morasco, B. J., Huckans, M. S., Morgan, T. R. M., Saperstein, S., Asghar, A., & Hauser, P. (2012) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2012.10.012 · Cited by 50 · see citing works
Pesarico, A. P., Sartori, G., Brüning, C. A., Mantovani, A. C., Duarte, T., Zeni, G. R., & Nogueira, C. W. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.03.049 · Cited by 41 · see citing works
Stepanichev, M. Y., Тишкина, А. О., Novikova, M. R., Levshina, I. P., Freiman, S. V., Onufriev, M. V., Levchenko, O. A., Лазарева, Н. А., & Gulyaeva, N. V. (2016) · Acta Neurobiologiae Experimentalis · doi:10.21307/ane-2017-031 · Cited by 39 · see citing works
Della, F. P., Abelaira, H. M., Réus, G. Z., Antunes, A. R., dos Santos, M. A. B., Zappellini, G., Steckert, A. V., Vuolo, F. S., Galant, L. S., Dal‐Pizzol, F., et al. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.09.018 · Cited by 38 · see citing works
Luo, Y., Kuang, S., Xue, L., & Yang, J. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.09.010 · Cited by 35 · see citing works
Preventing Relapse of Major Depression During Interferon-α Therapy for Hepatitis C—A Pilot Study
Gleason, O. C., Fucci, J. C., Yates, W. R., & Philipsen, M. A. (2007) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-9729-5 · Cited by 34 · see citing works
Пискунов, А. К., Stepanichev, M. Y., Тишкина, А. О., Novikova, M. R., Levshina, I. P., & Gulyaeva, N. V. (2016) · Metabolic Brain Disease · doi:10.1007/s11011-015-9785-7 · Cited by 27 · see citing works
Пискунов, А. К., Yakovlev, A. A., Stepanichev, M. Y., Onufriev, M. V., & Gulyaeva, N. V. (2011) · Neurochemical Journal · doi:10.1134/s1819712411020061 · Cited by 7 · see citing works
Grigoryan, G. A., & Gulyaeva, N. V. (2016) · PubMed · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
P2X7 Receptor Signaling in Stress and Depression
Ribeiro, D. E., Roncalho, A. L., Glaser, T., Ulrich, H., Wegener, G., & Joca, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112778 · Cited by 129 · see citing works
Glucocorticoids: Dr. Jekyll and Mr. Hyde of Hippocampal Neuroinflammation
Bolshakov, A. P., Tret’yakova, L. V., Kvichansky, A. A., & Gulyaeva, N. V. (2021) · Biochemistry (Moscow) · doi:10.1134/s0006297921020048 · Cited by 66 · see citing works
Guo, J., Qiu, T., Wang, L., Shi, L., Ai, M., Xia, Z., Peng, Z., Zheng, A., Li, X., & Kuang, L. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.802192 · Cited by 25 · see citing works
Avgana, H., Toledano, R. S., & Akirav, I. (2024) · Pharmaceuticals · doi:10.3390/ph17070846 · Cited by 11 · see citing works
Wang, L., Li, H., Zhao, Y., Sun, X., Qian, M., Shao, F., Lin, L., Hu, W., Dai, L., & Bao, H. (2025) · Phytotherapy Research · doi:10.1002/ptr.70106 · Cited by 9 · see citing works
Lazareva, N., Aniol, V. A., Stepanichev, M. Y., Манолова, А. О., & Gulyaeva, N. V. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.11.353
- Authors
- Stepanichev, M. Y., Peregud, D. I., Manolova, A. O., Lazareva, N. A., Onufriev, M. V., & Gulyaeva, N. V.
- Affiliations
- Russian Academy of Sciences (RU)
- Ministry of Health of the Russian Federation (RU)
- Corresponding author
- Stepanichev, M. Yu.
- Venue
- Biology Bulletin
- Publisher
- Pleiades Publishing Ltd
- Published
- 2018-03
- Volume
- 45
- Issue
- 2
- Pages
- 186-191
- ISSN
- 1062-3590 (ISSN-L)
- 1608-3059
- OpenAlex
- W2801479995
- Cited by
- 6
- References
- 38
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2019: 2
- FWCI
- 0.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biology Bulletin (publishedVersion)
- Funders
- Bauman Moscow State Technical University
- Russian Science Foundation
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- chronic mild stress, depression, inflammatory cytokines, interleukin-1 alpha, IL-1β, interleukin-6, TNF-α, cytokine gene expression, neuroinflammation, hippocampus, neocortex, brainstem, rat model
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