Programming Effects of Pubertal Lipopolysaccharide Treatment in Male and Female CD-1 Mice.

Puberty is a critical period of development marked by sexual, immune, and neural maturation. Exposure to stress during this period can lead to enduring changes in brain functioning and in behavior; however, the underlying mechanisms and the programming effects of stress during puberty remain unknown. Therefore, the objective of this study was to investigate the programming effects of pubertal immune challenge in response to a homotypic stressor later in life in CD-1 mice. Age and sex differences in the peripheral and central cytokine levels, along with sickness behavior and telemetry data, were analyzed following the secondary treatment. The results showed that pretreatment with LPS attenuated the immune response to a second homotypic challenge. Males pretreated with LPS during puberty and in early adulthood displayed an attenuated hypothermic response following the second LPS treatment compared with saline-pretreated controls, which is consistent with the attenuated peripheral IL-6 and IFN-γ concentrations. Females pretreated with LPS during puberty displayed lower IL-1ß, TNF-α, and IL-6 mRNA expression in the prefrontal cortex following the secondary immune challenge compared with saline controls. The results of this study show that exposure to LPS during puberty programs the peripheral and central immune responses, resulting in an attenuated immune response following a subsequent homotypic stressor. Thus, exposure to an immune challenge during puberty affects immune function later in life, which could permanently affect brain function and have implications on mental health.

Sex differences in the peripheral and central immune responses following lipopolysaccharide treatment in pubertal and adult CD-1 mice.

Puberty is a critical developmental period that is characterized by significant brain development. Exposure to stress during this time can alter brain functioning setting the stage for long-lasting behavioural outcomes. The objective of this study was to investigate age and sex differences in the peripheral and central immune responses, along with sickness behaviour, following immune stress. The results showed that LPS treatment increased serum cytokine levels and sickness symptoms in all mice. Pubertal males displayed increased IL-1ß concentrations at 2 h and increased IL-6 concentrations at 8 h post-treatment whereas increased concentrations of TNFα, IL-10, IL-12, IL-1ß, IFNγ, and IL-6 persisted at 8 and 24 h in adult females. Consistent with peripheral cytokines, pubertal males displayed greater IL-1ß, TNFα, and IL-6 mRNA expression in the prefrontal cortex at 2 h, whereas adult males expressed more of the aforementioned cytokines at 8 h compared to saline controls. Adult males also displayed greater IL-1ß mRNA expression compared to their female counterparts, and adult females displayed greater TNFα mRNA expression compared to their male counterparts. These results not only provide a better understanding of the age and sex differences in acute immune response, but also show important region- and time-specific differences in the response to an immune challenge, and that the peripheral immune response differs from the central response. This highlights the need to examine immune markers in both the periphery and the central nervous system for an accurate depiction of acute immune response following an immune challenge.

Corticosterone and immune cytokine characterization following environmental manipulation in female WKY rats.

This study investigated the effects of environmental manipulation on female Wistar Kyoto (WKY), an animal model of depression, and female Wistar rats. It explored the function of the hypothalamic-pituitary-adrenal axis (HPA) and immune system, as they have both been implicated in the pathophysiology of depression. A further goal was to characterize the immune cytokine concentrations of female WKY rats as this has, to our knowledge, never been documented. Animals were assigned to enriched, standard, or impoverished housing for four consecutive weeks. Following this, serum was collected at baseline and post-stress periods to measure the concentration of corticosterone, TNF-α, IL-1ß, and IL-10. WKY animals had significantly higher corticosterone levels at the post-stress time-point than their Wistar counterparts. WKY females in isolation tended to have the lowest corticosterone levels which may indicate that they prefer a solitary environment, a symptom of depression. We observed a significant decrease in TNF-α after enrichment in the Wistar strain. A similar decrease in TNF-α was found in the WKY strain, but there was no difference between environmental conditions. There was a significant increase in pre- to post-stress IL-10 level in both Wistar and WKY animals. WKY females had a significantly lower level of IL-1ß as compared to the Wistar animals at both pre- and post-stress time points. Given this strain difference, it is likely that the WKY rats had a dysregulated HPA axis which further influenced their circulating cytokine levels. Further studies are needed to examine how this pattern of findings plays a role in the pathophysiology of depression.