Differential responses of stressful elements to predatory exposure in behavior-lateralized mice

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Behavioral and Brain Functions Open Access

RESEARCH

Differential responses of stressful elements to predatory exposure in behavior‑lateralized mice Jiacai Yang1†, Lin Zhang1†, Jian‑ping Dai1, Jun Zeng1, Xiao‑xuan Chen1, Ze‑feng Xie1,2*‡, Kang‑sheng Li1*‡ and Yun Su1*‡ 

Abstract  Background:  Predatory stress as a psychological stressor can elicit the activation of the hypothalamic–pituitary– adrenal (HPA) axis, which is involved in the dialogue of the neuroimmunoendocrine network. The brain has been proven to regulate the activity of the HPA axis by way of lateralization. In the present study, we probed the pivotal ele‑ ments of the HPA circuitry including CRH, GR and a multifunctional cytokine in behavior-lateralized mice to determine their changes when the animals were subjected to predator exposure. Methods:  Behavior-lateralized mice were classified into left-pawed and right-pawed mice through a paw-preference test. Thereafter, mice in the acute stress group received a single 60-min cat exposure, and mice in the chronic group received daily 60-min cat exposure for 14 consecutive days. The plasma CS and TNF-α were determined by ELISA, the hypothalamic CRH mRNA and hippocampal GR mRNA were detected by real-time PCR, and the hippocampal GR protein was detected by western blot analysis. Results:  The results revealed that the levels of plasma CS were significantly elevated after chronic predatory expo‑ sure in both right-pawed and left-pawed mice; the right-pawed mice exhibited a higher plasma CS level than the left-pawed mice. Similarly, the acute or chronic cat exposure could induce the release of plasma TNF-α, and the leftpawed mice tended to show a higher level after the acute stress. Chronic stress significantly upregulated the expres‑ sion of hypothalamic CRH mRNA in both left-pawed and right-pawed mice. Normally, the left-pawed mice exhibited a higher GR expression in the hippocampus than the right-pawed mice. After the cat exposure, the expression of GR in both left-pawed and right-pawed mice was revealed to be greatly downregulated. Conclusion:  Our findings indicate that predatory stress can invoke a differential response of stressful elements in behavior-lateralized mice. Some of these responses shaped by behavioral lateralization might be helpful for facilitat‑ ing adaption to various stimuli. Keywords:  Predator, Stress, Behavior lateralization, HPA, Neuromodulation

*Correspondence: [email protected]; [email protected]; [email protected] † Jiacai Yang and Lin Zhang contributed equally to this work as first authors ‡ Ze-feng Xie, Kang-sheng Li and Yun Su contributed equally to this work 1 Department of Microbiology & Immunology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, People’s Republic of China Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat​iveco​mmons​.org/licen​ses/by/4.0/), which permits unres