Combined exposure to maternal high-fat diet and neonatal lipopolysaccharide disrupts stress-related signaling but normalizes spatial memory in juvenile rats

Both neonatal infections and exposure to maternal obesity are inflammatory stressors in early life linked to increased rates of psychopathologies related to mood and cognition. Epidemiological studies indicate that ne-onates born to mothers with obesity have a higher likelihood of developing neonatal infections, however effects on offspring physiology and behavior resulting from the combination of these stressors have yet to be investi-gated. The aim of this study was to explore immediate and persistent phenotypes resulting from neonatal lipopolysaccharide (nLPS) administration in rat offspring born to dams consuming a high-fat diet (HFD). Neural transcript abundance of genes involved with stress regulation and spatial memory were examined alongside related behaviors. At the juvenile age point, unlike offspring exposed to maternal HFD (mHFD) or nLPS alone, offspring with combined exposure to mHFD + nLPS displayed altered transcript abundances of stress-related genes in the ventral hippocampus (HPC) in a manner conducive to potentiating stress responses. For memory-related phenotypes, juveniles exposed to mHFD + nLPS exhibited normalized spatial memory and levels of memory-related gene expression in the dorsal HPC similar to control diet offspring, while control diet + nLPS, and mHFD offspring exhibited reduced levels of memory-related gene expression and impaired spatial memory. These findings suggest that dual exposure to unique inflammatory stressors in early life can disrupt neural stress regulation but normalize spatial memory processes.

Automated summary

Both neonatal infections and exposure to maternal obesity are inflammatory stressors in early life that can affect offspring's physiology and behavior. This study investigated the effects of neonatal lipopolysaccharide (nLPS) administration in rat offspring born to dams consuming a high-fat diet (HFD). The study found that dual exposure to maternal HFD and nLPS can disrupt neural stress regulation but normalize spatial memory processes.