Effects of Neonatal Lipopolysaccharide Injections at Various Developmental Stages on Long-term Behavioral Outcomes, Oxidative Stress, and Brain Histology in Rats

Abstract

The developing nervous system is highly susceptible to adverse events, particularly during critical periods. Disruptions, such as neonatal infections, can significantly alter brain structure and function, potentially contributing to the development of affective disorder-like behavior. In this study, we examined the effects of early lipopolysaccharide (LPS) exposure at two distinct postnatal days (PND). On PND 9 and 21, male and female rats were divided into two groups: one received intraperitoneal LPS injections at 0.2 mg/kg body weight, while the control group received intraperitoneal saline injections on the same days. Each group consisted of 5 rats per sex, resulting in 10 animals per group. After two months, both groups underwent a series of behavioral tests, oxidative stress assessments, and histological analyses. Myelination was evaluated using Luxol Fast Blue staining, while neuronal morphology and count were assessed using Cresyl Violet staining. The results revealed a reduction in the number of cells in the prefrontal cortex (PFC) and hippocampus (HPC), along with demyelination in the corpus callosum. These neuroanatomical changes were associated with depressive behaviors and memory impairments in both sexes, with a more pronounced effect in males. Furthermore, elevated oxidative stress levels were observed marked by significant increases in nitric oxide and lipid peroxidation markers in males. Sex differences were evident across the majority of measured outcomes. These findings highlight the critical role of early immune challenges in brain development and their potential contribution to neuropsychiatric disorders later in life.