Publication
Central and cardiac stress resilience consistently linked to integrated immuno‐neuroendocrine responses across stress models in male mice
Publisher:
Wiley
Date:
20-07-2022
DOI:
10.1111/EJN.15747
Abstract: Stress resilience, and behavioural and cardiovascular impacts of chronic stress, are theorised to involve integrated neuro‐endocrine/inflammatory/transmitter/trophin signalling. We tested for this integration, and whether behaviour/emotionality, together with myocardial ischaemic tolerance, are consistently linked to these pathways across erse conditions in male C57Bl/6 mice. This included Restraint Stress (RS), 1 h restraint/day for 14 days Chronic Unpredictable Mild Stress (CUMS), seven stressors randomised over 21 days Social Stress (SS), 35 days social isolation with brief social encounters in final 13 days and Control conditions (CTRL un‐stressed mice). Behaviour was assessed via open field (OFT) and sucrose preference (SPT) tests, and neurobiology from frontal cortex (FC) and hippoc al transcripts. Endocrine factors, and function and ischaemic tolerance in isolated hearts, were also measured. Model characteristics ranged from no behavioural or myocardial changes with homotypic RS, to increased emotionality and cardiac ischaemic injury (with apparently distinct endocrine/neurobiological profiles) in CUMS and SS models. Highly integrated expression of HPA axis, neuro‐inflammatory, BDNF, monoamine, GABA, cannabinoid and opioid signalling genes was confirmed across conditions, and consistent otentially causal correlations identified for (i) locomotor activity (noradrenaline, ghrelin FC Crhr1 , Tnfrsf1b , Il33 , Nfkb1 , Maoa , Gabra1 hippoc al Il33 ) (ii) thigmotaxis (adrenaline, leptin) (iii) anxiety‐like behaviour (adrenaline, leptin FC Tnfrsf1a hippoc al Il33 ) (iv) depressive‐like behaviour (ghrelin FC/hippoc al s100a8 ) and (v) cardiac stress‐resistance (noradrenaline, leptin FC Il33 , Tnfrsf1b , Htr1a , Gabra1 , Gabrg2 hippoc al Il33 , Tnfrsf1a , Maoa , Drd2 ). Data support highly integrated pathway responses to stress, and consistent adipokine, sympatho‐adrenergic, inflammatory and monoamine involvement in mood and myocardial disturbances across erse conditions.