Alpha lipoic acid ameliorates detrimental effects of maternal lipopolysaccharides exposure on prefrontal white matter in adult male offspring rats.

Background: Activation of the maternal immune system by lipopolysaccharide (LPS) increases the production of proinflammatory cytokines, free radicals, and reactive oxygen species (ROS), all of which play a significant role in the pathogenesis of many offspring neurodevelopmental disorders. Alpha Lipoic Acid (ALA) is a natural compound that has anti-inflammatory and antioxidant properties. This study was performed to assess the effect of prenatal exposure to LPS on the prefrontal white matter of rat offspring and evaluate the potential protective effects of ALA co-administration during pregnancy.

Methods: Pregnant Wistar rats were randomly divided into six groups (n = 6 each group): (1) control, (2) received LPS (100 μg/kg, intraperitoneally (IP) on gestational day 9.5 (GD 9.5), (3) received ALA (20 mg/kg) from GD1 to GD11, (4) LPS+ALA received LPS on GD9.5 and ALA from GD1 to GD11, (5 and 6) received LPS and ALA vehicle respectively. In each group, 21-day old male offspring (2 male pups from each mother) was harvested, and then their prefrontal white matter was separated and prepared for the ultrastructural, stereological, and molecular assays.

Results: In utero exposure to LPS led to a significant decrease in nerve cell counts, ultrastructural alterations in myelinated axons, and abnormal changes in genes expression of Sox10,Olig1,yrf,Wnt in the prefrontal of the rat offspring. Co-administration of ALA resulted in amelioration of those abnormal changes in the LPS rat offspring.

Conclusion: The findings of our preclinical study, explore that prenatal ALA treatment efficiently protects the nervous system against LPS induced abnormal changes in the offspring.