Lcn2 deficiency leads to social impairments independent of maternal immune activation

Both female and male offspring underwent a battery of behavioral assays. Lcn2 deletion and MIA independently induced deficits in social behavior and increased repetitive behavior phenotypes relevant to NDDs. However, their combination did not exacerbate these effects, suggesting an occlusion effect.

Importantly, the impact of Lcn2 deletion and MIA appeared to be specific to social and repetitive behavior, as no deficits were observed in the learning and memory task. To investigate potential shared molecular mechanisms, we performed RNA sequencing of the fetal forebrain 4 hours after the final LPS injection. This analysis revealed an overlapping group of differentially expressed genes in the Lcn2 KO and MIA groups, indicating convergence on similar transcriptional pathways that may underlie the observed behavioral phenotypes.

These results suggest that while Lcn2 may not mediate the pathological effects of prenatal immune challenge, it plays a critical role in normal brain development.