Abstract

Evaluating stress in laboratory animals is a key principle in animal welfare. Measuring corticosterone is a common method to assess stress in laboratory mice. There are, however, numerous methods to measure glucocorticoids with differences in sample matrix (e.g., plasma, urine) and quantification techniques (e.g., enzyme immunoassay or radioimmunoassay). Here, the authors present a mapping review and a searchable database, giving a complete overview of all studies mea­suring endogenous corticosterone in mice up to February 2018. For each study, information was recorded regarding mouse strain and sex; corticosterone sample matrix and quantification technique; and whether the study covered the research theme animal welfare, neuroscience, stress, inflammation, or pain (the themes of specific interest in our con­sortium). Using all database entries for the year 2012, an exploratory meta-regression was performed to determine the effect of predictors on basal corticosterone concentrations. Seventy-five studies were included using the predictors sex, time-since-lights-on, sample matrix, quantification technique, age of the mice, and type of control. Sex, time-since-lights-on, and type of control significantly affected basal corticosterone concentrations. The resulting database can be used, inter alia, for preventing unnecessary duplication of experiments, identifying knowledge gaps, and standardizing or heterogenizing methodologies. These results will help plan more efficient and valid experiments in the future and can answer new questions in silico using meta-analyses.

Highlights

  • Glucocorticoids are an important group of steroids that have multiple functions in mammals, including glucose metabolism and anti-inflammatory responses (Ralph and Tilbrook, 2016; Spiga et al, 2011)

  • Corticosterone secretion is part of the hypothalamus-pituitary-adrenal (HPA) axis, which consists of the hypothalamic paraventricular nucleus (HPN), the pituitary gland, and the adrenal cortex, which releases corticosterone into the bloodstream under the influence of adrenocorticotropic hormone (ACTH) from the pituitary gland

  • 5,448 were duplicate records, leaving 8,072 unique references to be screened for in- or exclusion. 2,894 references were excluded based on the reasons presented in Figure 1. 5,178 references were included for data extraction. 533 (10.3%) of the 5,178 references were identified as conference abstracts, while 4,645 references were full-length papers

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Summary

Introduction

Glucocorticoids are an important group of steroids that have multiple functions in mammals, including glucose metabolism and anti-inflammatory responses (Ralph and Tilbrook, 2016; Spiga et al, 2011). Corticosterone secretion is part of the hypothalamus-pituitary-adrenal (HPA) axis, which consists of the hypothalamic paraventricular nucleus (HPN), the pituitary gland, and the adrenal cortex, which releases corticosterone into the bloodstream under the influence of adrenocorticotropic hormone (ACTH) from the pituitary gland. There are multiple factors inherent to the organism that can influence baseline corticosterone concentrations including, but not limited to, sex, age, genetic background, circadian rhythm, and ultradian rhythm (Spiga et al, 2011; Windle et al, 1998; Jones et al, 1998; Spencer and Deak, 2017). A circadian rhythm is an approximately 24-hour cycle in physiological processes

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