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Prefrontal Cortex Regulates Chronic Stress‐Induced Cardiovascular Susceptibility
BACKGROUND: The medial prefrontal cortex is necessary for appropriate appraisal of stressful information, as well as coordinating visceral and behavioral processes. However, prolonged stress impairs medial prefrontal cortex function and prefrontal‐dependent behaviors. Additionally, chronic stress in...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951062/ https://www.ncbi.nlm.nih.gov/pubmed/31838941 http://dx.doi.org/10.1161/JAHA.119.014451 |
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author | Schaeuble, Derek Packard, Amy E. B. McKlveen, Jessica M. Morano, Rachel Fourman, Sarah Smith, Brittany L. Scheimann, Jessie R. Packard, Benjamin A. Wilson, Steven P. James, Jeanne Hui, David Y. Ulrich‐Lai, Yvonne M. Herman, James P. Myers, Brent |
author_facet | Schaeuble, Derek Packard, Amy E. B. McKlveen, Jessica M. Morano, Rachel Fourman, Sarah Smith, Brittany L. Scheimann, Jessie R. Packard, Benjamin A. Wilson, Steven P. James, Jeanne Hui, David Y. Ulrich‐Lai, Yvonne M. Herman, James P. Myers, Brent |
author_sort | Schaeuble, Derek |
collection | PubMed |
description | BACKGROUND: The medial prefrontal cortex is necessary for appropriate appraisal of stressful information, as well as coordinating visceral and behavioral processes. However, prolonged stress impairs medial prefrontal cortex function and prefrontal‐dependent behaviors. Additionally, chronic stress induces sympathetic predominance, contributing to health detriments associated with autonomic imbalance. Previous studies identified a subregion of rodent prefrontal cortex, infralimbic cortex (IL), as a key regulator of neuroendocrine‐autonomic integration after chronic stress, suggesting that IL output may prevent chronic stress‐induced autonomic imbalance. In the current study, we tested the hypothesis that the IL regulates hemodynamic, vascular, and cardiac responses to chronic stress. METHODS AND RESULTS: A viral‐packaged small interfering RNA construct was used to knockdown vesicular glutamate transporter 1 (vGluT1) and reduce glutamate packaging and release from IL projection neurons. Male rats were injected with a vGluT1 small interfering RNA‐expressing construct or GFP (green fluorescent protein) control into the IL and then remained as unstressed controls or were exposed to chronic variable stress. IL vGluT1 knockdown increased heart rate and mean arterial pressure reactivity, while chronic variable stress increased chronic mean arterial pressure only in small interfering RNA‐treated rats. In another cohort, chronic variable stress and vGluT1 knockdown interacted to impair both endothelial‐dependent and endothelial‐independent vasoreactivity ex vivo. Furthermore, vGluT1 knockdown and chronic variable stress increased histological markers of fibrosis and hypertrophy. CONCLUSIONS: Knockdown of glutamate release from IL projection neurons indicates that these cells are necessary to prevent the enhanced physiological responses to stress that promote susceptibility to cardiovascular pathophysiology. Ultimately, these findings provide evidence for a neurobiological mechanism mediating the relationship between stress and poor cardiovascular health outcomes. |
format | Online Article Text |
id | pubmed-6951062 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69510622020-01-10 Prefrontal Cortex Regulates Chronic Stress‐Induced Cardiovascular Susceptibility Schaeuble, Derek Packard, Amy E. B. McKlveen, Jessica M. Morano, Rachel Fourman, Sarah Smith, Brittany L. Scheimann, Jessie R. Packard, Benjamin A. Wilson, Steven P. James, Jeanne Hui, David Y. Ulrich‐Lai, Yvonne M. Herman, James P. Myers, Brent J Am Heart Assoc Original Research BACKGROUND: The medial prefrontal cortex is necessary for appropriate appraisal of stressful information, as well as coordinating visceral and behavioral processes. However, prolonged stress impairs medial prefrontal cortex function and prefrontal‐dependent behaviors. Additionally, chronic stress induces sympathetic predominance, contributing to health detriments associated with autonomic imbalance. Previous studies identified a subregion of rodent prefrontal cortex, infralimbic cortex (IL), as a key regulator of neuroendocrine‐autonomic integration after chronic stress, suggesting that IL output may prevent chronic stress‐induced autonomic imbalance. In the current study, we tested the hypothesis that the IL regulates hemodynamic, vascular, and cardiac responses to chronic stress. METHODS AND RESULTS: A viral‐packaged small interfering RNA construct was used to knockdown vesicular glutamate transporter 1 (vGluT1) and reduce glutamate packaging and release from IL projection neurons. Male rats were injected with a vGluT1 small interfering RNA‐expressing construct or GFP (green fluorescent protein) control into the IL and then remained as unstressed controls or were exposed to chronic variable stress. IL vGluT1 knockdown increased heart rate and mean arterial pressure reactivity, while chronic variable stress increased chronic mean arterial pressure only in small interfering RNA‐treated rats. In another cohort, chronic variable stress and vGluT1 knockdown interacted to impair both endothelial‐dependent and endothelial‐independent vasoreactivity ex vivo. Furthermore, vGluT1 knockdown and chronic variable stress increased histological markers of fibrosis and hypertrophy. CONCLUSIONS: Knockdown of glutamate release from IL projection neurons indicates that these cells are necessary to prevent the enhanced physiological responses to stress that promote susceptibility to cardiovascular pathophysiology. Ultimately, these findings provide evidence for a neurobiological mechanism mediating the relationship between stress and poor cardiovascular health outcomes. John Wiley and Sons Inc. 2019-12-14 /pmc/articles/PMC6951062/ /pubmed/31838941 http://dx.doi.org/10.1161/JAHA.119.014451 Text en © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Research Schaeuble, Derek Packard, Amy E. B. McKlveen, Jessica M. Morano, Rachel Fourman, Sarah Smith, Brittany L. Scheimann, Jessie R. Packard, Benjamin A. Wilson, Steven P. James, Jeanne Hui, David Y. Ulrich‐Lai, Yvonne M. Herman, James P. Myers, Brent Prefrontal Cortex Regulates Chronic Stress‐Induced Cardiovascular Susceptibility |
title | Prefrontal Cortex Regulates Chronic Stress‐Induced Cardiovascular Susceptibility |
title_full | Prefrontal Cortex Regulates Chronic Stress‐Induced Cardiovascular Susceptibility |
title_fullStr | Prefrontal Cortex Regulates Chronic Stress‐Induced Cardiovascular Susceptibility |
title_full_unstemmed | Prefrontal Cortex Regulates Chronic Stress‐Induced Cardiovascular Susceptibility |
title_short | Prefrontal Cortex Regulates Chronic Stress‐Induced Cardiovascular Susceptibility |
title_sort | prefrontal cortex regulates chronic stress‐induced cardiovascular susceptibility |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951062/ https://www.ncbi.nlm.nih.gov/pubmed/31838941 http://dx.doi.org/10.1161/JAHA.119.014451 |
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