Distinct immune and transcriptomic profiles in dominant versus subordinate males in mouse social hierarchies.

Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. In particular, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed a relatively higher expression of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed relatively higher expression of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed relatively higher expression of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift immune profiles and peripheral gene expression to match their contextual needs.

Acetaminophen disrupts memory in object recognition and increases extracellular signal-regulated kinase phosphorylation in male mice.

Acetaminophen (also known as paracetamol) is a commonly used over-the-counter pain medication, but recent evidence suggests that a single exposure or prenatal exposure may have significant behavioral effects. This investigation aimed to determine whether acetaminophen could disrupt memory formation in an object-recognition task and to quantify potential changes in memory-related signaling cascades in the hippocampus of mice after acetaminophen administration. Using male mice, we examined the effect of a single subcutaneous injection of acetaminophen on the object-recognition task, a single-trial, hippocampus-dependent memory task. We also investigated potential changes in the activation of extracellular signal-regulated kinase (ERK) in the dorsal mouse hippocampus 1 hr after a subcutaneous injection of acetaminophen. We found that 50 mg/kg and 100 mg/kg interfered with performance in the object-recognition memory task, whereas 10 mg/kg did not. We also found that a single 50 mg/kg injection of acetaminophen significantly increased p42 ERK phosphorylation in the dorsal mouse hippocampus. Overall, these results suggest that a single dose of acetaminophen can have significant effects on memory and alters signaling kinases critical for memory consolidation. Further work is needed to determine the involved mechanisms. (PsycINFO Database Record (c) 2018 APA, all rights reserved).