Detection of Disturbances in Maturation Trajectory of Brain Structure by Means of Linear Models

This study investigated the influence of early-life lipopolysaccharide (LPS) injection on the maturation of non-neuronal elements in limbic structures. We administered LPS to Wistar rats on postnatal days (PD) 3 and 5, evaluating morphological characteristics of microglia and astrocytes in the hippocampus and amygdala at the age of adolescence. We build linear models on the datasets of control animals to perform the maturation of glia at the period from PD28 to PD42 during normal conditions. For building models, we used 70% of dataset, and least 30% we used for model validation. Our models predicted the age of animal by the state of glia in the brain structure. The correlations of predicted and actual ages were statistically significant and equaled approximately 0.8–0.9. And then we used these models to predict ages of LPS-treated animals. There were no correlations between predicted and actual ages for the females exposed to early-life LPS injection. For the males we found negative correlations in CA1 hippocampal subfield and dentata gyrus hilus. These findings indicate disturbances of the trajectory of glia maturation caused by early-life stress. Our work highlights notable sex differences in response to early-life stress, suggesting different mechanisms of vulnerability and resilience between males and females.