New findings in immune epigenomics are a return on investment

Abstract

Stress during critical periods of neurodevelopment is associated with an increased risk of developing stress-related psychiatric disorders, which are more common in women than men. Hippocampal neurogenesis (the birth of new neurons) is vulnerable to maternal separation (MS) and inflammatory stressors, and emerging evidence suggests that hippocampal neurogenesis is more sensitive to stress in the ventral hippocampus (vHi) than in the dorsal hippocampus (dHi). Although research into the effects of MS stress on hippocampal neurogenesis is well documented in male rodents, the effect in females remains underexplored. Similarly, reports on the impact of inflammatory stressors on hippocampal neurogenesis in females are limited, especially when female bias in the prevalence of stress-related psychiatric disorders begins to emerge. Thus, in this study we investigated the effects of MS followed by an inflammatory stressor (lipopolysaccharide, LPS) in early adolescence on peripheral and hippocampal inflammatory responses and hippocampal neurogenesis in juvenile female rats. We show that MS enhanced an LPS-induced increase in the pro-inflammatory cytokine IL-1β in the vHi but not in the dHi. However, microglial activation was similar following LPS alone or MS alone in both hippocampal regions, while MS prior to LPS reduced microglial activation in both dHi and vHi. The production of new neurons was unaffected by MS and LPS. MS and LPS independently reduced the dendritic complexity of new neurons, and MS exacerbated LPS-induced reductions in the complexity of distal dendrites of new neurons in the vHi but not dHi. These data highlight that MS differentially primes the physiological response to LPS in the juvenile female rat hippocampus.