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Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway
Evidence indicates that adverse experiences in early life may be a factor for immune disturbances leading to the depression in adulthood. Recently, a pivotal role in the pathogenesis of depression has been assigned to the activation of the brain Nod-like receptor pyrin-containing 3 (NLRP3) inflammas...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614144/ https://www.ncbi.nlm.nih.gov/pubmed/30610610 http://dx.doi.org/10.1007/s12035-018-1458-1 |
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author | Trojan, Ewa Chamera, Katarzyna Bryniarska, Natalia Kotarska, Katarzyna Leśkiewicz, Monika Regulska, Magdalena Basta-Kaim, Agnieszka |
author_facet | Trojan, Ewa Chamera, Katarzyna Bryniarska, Natalia Kotarska, Katarzyna Leśkiewicz, Monika Regulska, Magdalena Basta-Kaim, Agnieszka |
author_sort | Trojan, Ewa |
collection | PubMed |
description | Evidence indicates that adverse experiences in early life may be a factor for immune disturbances leading to the depression in adulthood. Recently, a pivotal role in the pathogenesis of depression has been assigned to the activation of the brain Nod-like receptor pyrin-containing 3 (NLRP3) inflammasome. We investigated the impact of chronic treatment with antidepressant drugs on the behavioral disturbances and the levels of proinflammatory factors in the hippocampus and frontal cortex of adult male rats after prenatal stress exposure. Next, we explored the involvement of the NLRP3 inflammasome-related pathways in the mechanism of antidepressant action. Our study confirmed that chronic antidepressant treatment attenuated depression-like disturbances and exerted an anxiolytic action. All antidepressants diminished the prenatal stress-induced increase in IL-1β in both brain areas, while IL-18 only in the hippocampus. Moreover, tianeptine administration diminished the increase in CCR2 levels in both brain areas, while in the hippocampus, tianeptine, along with venlafaxine CCL2 and iNOS levels. Next, we observed that in the hippocampus, tianeptine and fluoxetine suppressed upregulation of TLR4. Furthermore, venlafaxine suppressed NFкB p65-subunit phosphorylation, while fluoxetine enhanced the IкB level. Importantly, in the hippocampus, all antidepressants normalized evoked by stress changes in caspase-1 level, while tianeptine and venlafaxine also affect the levels of ASC and NLRP3 subunits. Our results provide new evidence that chronic administration of antidepressants exerts anti-inflammatory effects more pronounced in the hippocampus, through suppression of the NLRP3 inflammasome activation. These effects are accompanied by an improvement in the behavioral dysfunctions evoked by prenatal stress. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1458-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6614144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-66141442019-07-28 Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway Trojan, Ewa Chamera, Katarzyna Bryniarska, Natalia Kotarska, Katarzyna Leśkiewicz, Monika Regulska, Magdalena Basta-Kaim, Agnieszka Mol Neurobiol Article Evidence indicates that adverse experiences in early life may be a factor for immune disturbances leading to the depression in adulthood. Recently, a pivotal role in the pathogenesis of depression has been assigned to the activation of the brain Nod-like receptor pyrin-containing 3 (NLRP3) inflammasome. We investigated the impact of chronic treatment with antidepressant drugs on the behavioral disturbances and the levels of proinflammatory factors in the hippocampus and frontal cortex of adult male rats after prenatal stress exposure. Next, we explored the involvement of the NLRP3 inflammasome-related pathways in the mechanism of antidepressant action. Our study confirmed that chronic antidepressant treatment attenuated depression-like disturbances and exerted an anxiolytic action. All antidepressants diminished the prenatal stress-induced increase in IL-1β in both brain areas, while IL-18 only in the hippocampus. Moreover, tianeptine administration diminished the increase in CCR2 levels in both brain areas, while in the hippocampus, tianeptine, along with venlafaxine CCL2 and iNOS levels. Next, we observed that in the hippocampus, tianeptine and fluoxetine suppressed upregulation of TLR4. Furthermore, venlafaxine suppressed NFкB p65-subunit phosphorylation, while fluoxetine enhanced the IкB level. Importantly, in the hippocampus, all antidepressants normalized evoked by stress changes in caspase-1 level, while tianeptine and venlafaxine also affect the levels of ASC and NLRP3 subunits. Our results provide new evidence that chronic administration of antidepressants exerts anti-inflammatory effects more pronounced in the hippocampus, through suppression of the NLRP3 inflammasome activation. These effects are accompanied by an improvement in the behavioral dysfunctions evoked by prenatal stress. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1458-1) contains supplementary material, which is available to authorized users. Springer US 2019-01-04 2019 /pmc/articles/PMC6614144/ /pubmed/30610610 http://dx.doi.org/10.1007/s12035-018-1458-1 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Trojan, Ewa Chamera, Katarzyna Bryniarska, Natalia Kotarska, Katarzyna Leśkiewicz, Monika Regulska, Magdalena Basta-Kaim, Agnieszka Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway |
title | Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway |
title_full | Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway |
title_fullStr | Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway |
title_full_unstemmed | Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway |
title_short | Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway |
title_sort | role of chronic administration of antidepressant drugs in the prenatal stress-evoked inflammatory response in the brain of adult offspring rats: involvement of the nlrp3 inflammasome-related pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614144/ https://www.ncbi.nlm.nih.gov/pubmed/30610610 http://dx.doi.org/10.1007/s12035-018-1458-1 |
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