Cargando…
Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man
Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of eit...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070549/ https://www.ncbi.nlm.nih.gov/pubmed/30068974 http://dx.doi.org/10.1038/s41398-018-0196-5 |
_version_ | 1783343688416493568 |
---|---|
author | Santi, A. Bot, M. Aleman, A. Penninx, B. W. J. H. Aleman, I. Torres |
author_facet | Santi, A. Bot, M. Aleman, A. Penninx, B. W. J. H. Aleman, I. Torres |
author_sort | Santi, A. |
collection | PubMed |
description | Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures. In mice, anxiety-like responses to predator were inversely related to circulating IGF-I levels. Other indicators of mood regulation such as sensitivity to dexamethasone suppression and expression levels of blood and brain FK506 binding protein 5 (FKBP5), a co-chaperone of the glucocorticoid receptor that regulates its activity, were also associated to circulating IGF-I. Indeed, brain FKBP5 expression in mice was stimulated by IGF-I. In addition, we observed in a large human cohort (n = 2686) a significant relationship between plasma IGF-I and exposure to recent stressful life events, while FKBP5 expression in blood cells was significantly associated to plasma IGF-I levels. Collectively, these data indicate that circulating IGF-I appears to be involved in mood homeostasis across different species. Furthermore, the data in mice allow us to indicate that IGF-I may be acting at least in part by modulating FKBP5 expression. |
format | Online Article Text |
id | pubmed-6070549 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60705492018-08-02 Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man Santi, A. Bot, M. Aleman, A. Penninx, B. W. J. H. Aleman, I. Torres Transl Psychiatry Article Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures. In mice, anxiety-like responses to predator were inversely related to circulating IGF-I levels. Other indicators of mood regulation such as sensitivity to dexamethasone suppression and expression levels of blood and brain FK506 binding protein 5 (FKBP5), a co-chaperone of the glucocorticoid receptor that regulates its activity, were also associated to circulating IGF-I. Indeed, brain FKBP5 expression in mice was stimulated by IGF-I. In addition, we observed in a large human cohort (n = 2686) a significant relationship between plasma IGF-I and exposure to recent stressful life events, while FKBP5 expression in blood cells was significantly associated to plasma IGF-I levels. Collectively, these data indicate that circulating IGF-I appears to be involved in mood homeostasis across different species. Furthermore, the data in mice allow us to indicate that IGF-I may be acting at least in part by modulating FKBP5 expression. Nature Publishing Group UK 2018-08-01 /pmc/articles/PMC6070549/ /pubmed/30068974 http://dx.doi.org/10.1038/s41398-018-0196-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Santi, A. Bot, M. Aleman, A. Penninx, B. W. J. H. Aleman, I. Torres Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man |
title | Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man |
title_full | Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man |
title_fullStr | Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man |
title_full_unstemmed | Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man |
title_short | Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man |
title_sort | circulating insulin-like growth factor i modulates mood and is a biomarker of vulnerability to stress: from mouse to man |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070549/ https://www.ncbi.nlm.nih.gov/pubmed/30068974 http://dx.doi.org/10.1038/s41398-018-0196-5 |
work_keys_str_mv | AT santia circulatinginsulinlikegrowthfactorimodulatesmoodandisabiomarkerofvulnerabilitytostressfrommousetoman AT botm circulatinginsulinlikegrowthfactorimodulatesmoodandisabiomarkerofvulnerabilitytostressfrommousetoman AT alemana circulatinginsulinlikegrowthfactorimodulatesmoodandisabiomarkerofvulnerabilitytostressfrommousetoman AT penninxbwjh circulatinginsulinlikegrowthfactorimodulatesmoodandisabiomarkerofvulnerabilitytostressfrommousetoman AT alemanitorres circulatinginsulinlikegrowthfactorimodulatesmoodandisabiomarkerofvulnerabilitytostressfrommousetoman |