Abstract

Physiological responses to psychological stressors are protective in acute fight or flight situations; however, there is increasing evidence suggesting the detrimental impact of chronic psychological stress on disease. Chronic stress has been associated with inflammation, poor prognosis, increased morbidity, and poor outcome in many diseases including atherosclerosis, cancer, and pulmonary disease. Given the systemic impact of stress, and the role of the hematopoietic system as a rapid responder to homeostatic insults, we hypothesized that early blood profile changes and biochemical alterations could be detected in a model of chronic stress. To test this hypothesis, a variation of the chronic unpredictable stress (CUS) model was employed. Following 10 days of CUS, C57BL/6 mice exhibited a chronic-stress-associated corticosterone profile. Complete blood count (CBC) revealed mild normochromic, normocytic anemia, and reduced monocyte and lymphocyte count. Serum analysis demonstrated hypoferremia with unchanged total iron binding capacity and serum ferritin levels. These findings are consistent with clinical diagnostic parameters for anemia of chronic disease and indicate that CUS results in significant changes in blood and serum biochemical profile in C57BL/6 mice. These studies identify early changes in blood parameters in response to CUS and identify hematopoietic and biochemical alterations that are often associated with increased morbidity in patients experiencing chronic-stress-associated mental health disease.

Highlights

  • Chronic stress has been associated with chronic illness such as obesity and depression and contributes to worse prognosis, accelerated disease progression, and poorer survival in many diseases including lung pathologies [1, 2], cardiovascular disease [3] [reviewed in Refs. [4, 5]], and cancer [reviewed in Ref. [6]]

  • Using a variation of the chronic unpredictable stress (CUS) model, we demonstrated changes in serum corticosterone levels associated with a chronic stress response and dysregulation of the hypothalamic–pituitary–adrenal axis (HPA) often found in patients with depressive mood [13] and anxiety [14] or in caregivers [15]

  • This study demonstrates that CUS leads to early and clinically relevant blood profile and biochemical changes in C57BL/6 mice that are readily detected in live animals following 10 days of CUS

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Summary

Introduction

Chronic stress has been associated with chronic illness such as obesity and depression and contributes to worse prognosis, accelerated disease progression, and poorer survival in many diseases including lung pathologies [1, 2], cardiovascular disease [3] [reviewed in Refs. [4, 5]], and cancer [reviewed in Ref. [6]]. We tested the hypothesis that early blood profile changes and biochemical alterations could be detected in a model of chronic stress. We demonstrated significant blood profile changes that were readily detected via complete blood count (CBC) and serum iron analyses. These studies are significant in that they identify early hematopoietic and biochemical parameters altered by stress in C57BL/6 mice. These findings provide insight into potential factors that may contribute to chronic psychological stress-induced exacerbation of disease

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