Open AccessPrefrontal Cortex Regulates Chronic Stress‐Induced Cardiovascular Susceptibility
Author(s) -
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.,
UlrichLai Yvonne M.,
Herman James P.,
Myers Brent
Publication year - 2019
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.119.014451
Subject(s) - gene knockdown , prefrontal cortex , chronic stress , glutamate receptor , neuroscience , medicine , endocrinology , small interfering rna , biology , rna , receptor , gene , biochemistry , cognition
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 ( vG luT1) and reduce glutamate packaging and release from IL projection neurons. Male rats were injected with a vG luT1 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 vG luT1 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, vG luT1 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.