TY - JOUR
T1 - Autonomic and redox imbalance correlates with T-Lymphocyte inflammation in a model of chronic social defeat stress
AU - Moshfegh, Cassandra M.
AU - Elkhatib, Safwan K.
AU - Collins, Christopher W.
AU - Kohl, Allison J.
AU - Case, Adam J.
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) R00HL123471 and the Mary G. and George W. White Fund for Medical Research to AC. The University of Nebraska DNA Sequencing Core receives partial support from the National Institute for General Medical Science (NIGMS) INBRE-P20GM103427-14 and COBRE-1P30GM110768-01 grants as well as The Fred and Pamela Buffett Cancer Center Support Grant-P30CA036727. We thank the Bioinformatics and Systems Biology Core at UNMC for providing single-cell RNA sequencing data analysis services, which receives support from Nebraska Research Initiative (NRI) and National Institutes of Health (NIH; 2P20GM103427 and 5P30CA036727).
Publisher Copyright:
© 2019 Moshfegh, Elkhatib, Collins, Kohl and Case.
PY - 2019/4/30
Y1 - 2019/4/30
N2 - Patients diagnosed with post-traumatic stress disorder (PTSD) are at a significantly elevated risk of developing comorbid inflammatory conditions, but the mechanisms underlying this predilection remain unclear. Our previous work has shown that T-lymphocytes exposed to elevated levels of norepinephrine (NE) displayed a pro-inflammatory signature reminiscent of an autoreactive phenotype. With this, we hypothesized that the increased sympathetic tone observed during psychological trauma may be promoting pro-inflammatory T-lymphocytes, which causes a predisposition to comorbid inflammatory conditions. Here, we examined the consequences of psychological trauma on splenic T-lymphocytes using a mouse model of repeated social defeat stress. Social defeat led to anxiety-like and depression-like behavior as has been previously described. The spleens of socially-defeated mice showed significant elevations of NE, tyrosine hydroxylase (TH), and acetylcholinesterase (ACHE) levels, which appeared to be due in part to increased expression within T-lymphocytes. Additionally, T-lymphocytes from stressed animals showed higher levels of pro-inflammatory cytokines and mitochondrial superoxide. Interestingly, in this model system, close associations exist within splenic T-lymphocytes amid the autonomic, inflammatory, and redox environments, but these only weakly correlate with individual behavioral differences among animals suggesting the psychological and physiological manifestations of trauma may not be tightly coupled. Last, we describe, for the first time, elevations in calprotectin levels within T-lymphocytes and in circulation of psychologically stressed animals. Calprotectin correlated with both behavioral and physiological changes after social defeat, suggesting the potential for a new biological marker and/or therapeutic target for psychological trauma and its inflammatory comorbidities.
AB - Patients diagnosed with post-traumatic stress disorder (PTSD) are at a significantly elevated risk of developing comorbid inflammatory conditions, but the mechanisms underlying this predilection remain unclear. Our previous work has shown that T-lymphocytes exposed to elevated levels of norepinephrine (NE) displayed a pro-inflammatory signature reminiscent of an autoreactive phenotype. With this, we hypothesized that the increased sympathetic tone observed during psychological trauma may be promoting pro-inflammatory T-lymphocytes, which causes a predisposition to comorbid inflammatory conditions. Here, we examined the consequences of psychological trauma on splenic T-lymphocytes using a mouse model of repeated social defeat stress. Social defeat led to anxiety-like and depression-like behavior as has been previously described. The spleens of socially-defeated mice showed significant elevations of NE, tyrosine hydroxylase (TH), and acetylcholinesterase (ACHE) levels, which appeared to be due in part to increased expression within T-lymphocytes. Additionally, T-lymphocytes from stressed animals showed higher levels of pro-inflammatory cytokines and mitochondrial superoxide. Interestingly, in this model system, close associations exist within splenic T-lymphocytes amid the autonomic, inflammatory, and redox environments, but these only weakly correlate with individual behavioral differences among animals suggesting the psychological and physiological manifestations of trauma may not be tightly coupled. Last, we describe, for the first time, elevations in calprotectin levels within T-lymphocytes and in circulation of psychologically stressed animals. Calprotectin correlated with both behavioral and physiological changes after social defeat, suggesting the potential for a new biological marker and/or therapeutic target for psychological trauma and its inflammatory comorbidities.
KW - Behavior
KW - Calprotectin
KW - IL-17
KW - IL-6
KW - Immune
KW - Norepinephrine
KW - PTSD
KW - Post-traumatic stress disorder
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U2 - 10.3389/fnbeh.2019.00103
DO - 10.3389/fnbeh.2019.00103
M3 - Article
C2 - 31139062
AN - SCOPUS:85067117277
VL - 13
JO - Frontiers in Behavioral Neuroscience
JF - Frontiers in Behavioral Neuroscience
SN - 1662-5153
M1 - 103
ER -