Effects of pair-housing pubertal and adult male and female mice on LPS-induced age-dependent immune responses: A potential role for the gut microbiota.

Puberty is a critical period of development that is marked by the maturation of the stress and immune systems. There are marked age and sex differences in peripheral and central inflammatory responses to an immune challenge between pubertal and adult mice. Given the strong link between the gut microbiome and immune system, it is possible that the age and sex differences in immune responses are mediated by age and sex differences in gut microbial composition. The current study investigated whether cohousing adult and pubertal CD1 mice through three weeks of pair-housing, with the potential for microbiome exchange via coprophagy and other close contact, could mitigate age-dependent immune responses. Cytokine concentrations in the blood and cytokine mRNA expression in the brain were assessed following exposure to the immune challenge lipopolysaccharide (LPS). The results show that all mice displayed increased cytokine concentrations in serum and central cytokine mRNA expression in the hippocampus, hypothalamus and prefrontal cortex (PFC) at eight hours following LPS treatment. Pubertal male and female mice, that were pair-housed with a pubertal counterpart, displayed lower cytokine concentrations in serum and lower cytokine mRNA expression in the brain compared to adult mice that were pair-housed with an adult counterpart. However, when adult and pubertal mice were pair-housed, the age differences in both peripheral cytokine concentrations and central cytokine mRNA expression were mitigated. We also found that pair-housing adult and pubertal mice eliminated the age difference in gut bacterial diversity. These results suggest that microbial composition could be involved in modulating these age-associated immune responses and thus may represent a potential therapeutic target.

Single cell force spectroscopy of erythrocytes at physiological and febrile temperatures reveals mechano-modulatory effects of atorvastatin.

RBCs are mechanically active cells and constantly deform as they circulate through vasculature. Their mechanical properties can be significantly altered by various pathophysiological conditions, and the alterations in RBC mechanics can, in turn, have functional consequences. Although numerous mechanical studies have been conducted on RBCs, surprisingly, strain-rate and temperature dependent mechanics of RBCs have not been systematically examined, and current data is primarily based on measurements at room temperature. Here, we have used state-of-the-art single-cell optical tweezers to probe atorvastatin-induced changes of RBC mechanics and its strain-rate dependency at physiologically and medically relevant temperatures. Our data indicate that RBC mechanics is strain-rate and temperature dependent, and atorvastatin treatment softens RBCs at physiological temperature, but not at febrile temperature. The observed mechanical change is a notable side effect of the drug in some therapeutic applications. However, the mechano-modulatory effects of atorvastatin on erythrocytes at physiological temperature might offer new therapeutic possibilities for diseases related to blood cell mechanics.

Probiotic consumption during puberty mitigates LPS-induced immune responses and protects against stress-induced depression- and anxiety-like behaviors in adulthood in a sex-specific manner.

Puberty/adolescence is a significant period of development and a time with a high emergence of psychiatric disorders. During this period, there is increased neuroplasticity and heightened vulnerability to stress and inflammation. The gut microbiome regulates stress and inflammatory responses and can alter brain chemistry and behaviour. However, the role of the gut microbiota during pubertal development remains largely uninvestigated. The current study examined gut manipulation with probiotics during puberty in CD1 mice on lipopolysaccharide (LPS)-induced immune responses and enduring effects on anxiety- and depression-like behaviours and stress-reactivity in adulthood. Probiotics reduced LPS-induced sickness behaviour at 12 h in females and at 48 h following LPS treatment in males. Probiotics also reduced LPS-induced changes in body weight at 48 h post-treatment in females. Probiotic treatment also prevented LPS-induced increases in pro- and anti-inflammatory peripheral cytokines at 8 h following LPS treatment, reduced central cytokine mRNA expression in the hypothalamus, hippocampus and PFC, and prevented LPS-induced changes to in the gut microbiota. A single exposure to LPS during puberty resulted in enduring depression-like behaviour in female mice, and anxiety-like behaviour in male mice in adulthood. However, pubertal exposure to probiotics prevented enduring LPS-induced depression-like behaviour in females and anxiety-like behaviors in males. Moreover, probiotics altered toll-like receptor-4 activity in the paraventricular nucleus of the hypothalamus (PVN) in males in response to a novel stressor in adulthood. Our results suggest that the gut microbiome plays an important role in pubertal neurodevelopment. These findings indicate that exposure to probiotics during puberty mitigates inflammation and decreases stress-induced vulnerabilities to emotional behaviours later in life, in a sex-specific manner.